Thiaiazolyl benzamides

ABSTRACT

N-Aryl benzamides wherein the aryl group is a nitrogen containing heterocycle are useful as selective herbicidal agents. Compositions containing the novel benzamides and a herbicidal method of selective weed control are disclosed.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a division of Ser. No. 685,922, filed Dec. 24, 1984,now U.S. Pat. No. 4,636,243 which is a division of Ser. No. 510,699,filed July 5, 1983, now U.S. Pat. No. 4,515,625; which is a division ofSer. No. 302,323, filed Sept. 14, 1981, now U.S. Pat. No. 4,416,683,which is a continuation-in-part of Ser. No. 187,675, filed Sept. 16,1980, now abandoned.

BACKGROUND OF THE INVENTION

The use of herbicides to selectively control the growth of unwantedvegetation in crops grown for human and domestic animal consumption iswell established. A number of problems are associated with the continueduse of chemical herbicides however, including environmental pollution,crop tolerance, weed resistance, as well as economic considerations.Accordingly, the search continues for new herbicides which areeconomical and which are selectively toxic to unwanted vegetation.

A wide variety of benzamides are known in the art. Ward, for example, inU.S. Pat. No. 4,141,984, discloses certain thiadiazolyl benzamides whichare said to possess insecticidal efficacy. Kaplan et al., in U.S. Pat.No. 4,189,495, disclose a series of 2-methoxybenzamides which allegedlypossess pharmacological activity.

An object of the present invention is to provide a novel class of N-arylbenzamides which are potent herbicides. A further object is to providecompositions containing such compounds, as well as a method for theiruse.

SUMMARY OF THE INVENTION

The present invention relates to herbicidal benzamide derivatives, andmore particularly to N-aryl benzamides of the formula ##STR1## wherein:Z is oxygen or sulfur;

R¹ is hydrogen, halogen, C₁ -C₄ alkyl, or C₁ -C₄ alkoxy;

R² is hydrogen, halogen, C₁ -C₄ alkyl, C₁ -C₄ alkoxy, C₁ -C₄ alkylthioor trifluoromethyl;

R³ is hydrogen, halogn, C₁ -C₄ alkyl, C₁ -C₄ alkoxy or C₁ -C₄ alkylthio;provided that when one of R¹, R² or R³ is alkyl, one or both of theother phenyl substituents is other than hydrogen; and when R² istrifluoromethyl, one or both of R¹ and R³ is other than hydrogen;

R⁴ is an aryl group selected from ##STR2## wherein: R is hydrogen or C₁-C₄ alkyl;

A is CH or N and B is CH or N, provided that one of A and B is CH andthe other is N;

X is NH, O or S;

R⁵ is hydrogen, ##STR3## wherein: R⁶ is hydrogen, C₁ -C₄ alkyl, C₂ -C₄alkenyl, C₂ -C₄ alkynyl, C₁ -C₆ alkoxy, or C₁ -C₆ alkylthio;

y is an integer from 0 to 5;

R⁷ and R⁸ independently are hydrogen, C₁ -C₁₃ alkyl, halo-C₁ -C₁₃ alkyl,C₂ -C₁₃ alkenyl, C₂ -C₁₃ alkynyl, C₁ -C₆ alkoxy, C₁ -C₆ -alkylthio, C₁-C₄ alkoxy-C₁ -C₆ alkyl, C₁ -C₄ alkylthio-C₁ -C₆ alkyl, C₂ -C₄alkanoyloxy-C₁ -C₆ alkyl, ##STR4## in which m is an integer from 0 to 4;n is zero or 1; R⁹ and R¹⁰ independently are hydrogen, halogen, C₁ -C₄alkyl or C₂ -C₄ alkenyl; Q¹ and Q² independently are CH₂, --(CH₂)_(n)--O-- or --(CH₂)_(n) --S--; provided that when Q¹ and Q² are both otherthan CH₂, y is other than zero; and provided that R⁵ is hydrogen onlywhen R⁴ is ##STR5## and provided that R² and R³ are other than hydrogenwhen R⁴ is ##STR6## and the agronomically acceptable salts thereof.

A particularly valuable class of herbicidal benzamides provided by thisinvention are defined by the above formula wherein Z is oxygen, R⁴ is##STR7## R⁵ is hydrogen, ##STR8## in which R⁶ and R⁷ independently arehydrogen, C₁ -C₄ alkyl, C₂ -C₄ alkenyl; or C₂ -C₄ alkynyl;

y is an integer from 0 to 4;

R⁸ is as defined other than alkoxy, alkylthio or alkanoyloxy; and

Q¹ and Q² both are --CH₂ --.

Preferred compounds are those defined by the above formula wherein oneor more of the following characteristics apply;

(a) Z is oxygen;

(b) R is hydrogen;

(c) R¹ is hydrogen and R² and R³ independently are C₁ -C₄ alkoxy, C₁ -C₄alkyl, or C₁ -C₄ alkylthio, especially when attached at the 2 and6-positions;

(d) R¹ is hydrogen and R² and R³ independently are C₁ -C₄ alkoxy,preferably attached at the 2 and 6-positions;

(e) R¹ is hydrogen, R² is 2-methoxy or 2-ethoxy and R³ is 6-methoxy or6-ethoxy;

(f) R⁴ is ##STR9##

(g) R⁴ is ##STR10##

(h) R⁴ is ##STR11##

(i) R⁴ is ##STR12##

(j) R⁵ is ##STR13## wherein R⁶ is C₁ -C₄ alkyl;

(k) R⁵ is ##STR14## wherein one or both of R⁶ and R⁷ independently areC₁ -C₄ alkyl;

(l) R⁵ is ##STR15## wherein one or both of R⁶ and R⁷ independently areC₁ -C₄ alkyl and R⁸ is C₁ -C₁₃ alkyl or cycloalkyl of the formula##STR16##

(m) R⁵ is ##STR17## wherein R⁶ is C₁ -C₄ alkyl and R⁹ and R¹⁰ both arehydrogen;

(n) R⁵ is 1-ethyl-1-methylpropyl;

(o) R⁵ is 1,1-dimethylethyl;

(p) R⁵ is 1-ethylcyclohexyl.

Also provided by this invention are formulations comprising a benzamideof the above general formula together with an agronomically-acceptablecarrier, diluent, or adjuvant therefor. Compositions comprising abenzamide as defined above in combination with one or more othercompatible herbicides are also contemplated.

Additionally provided by the invention is a method for controlling thegrowth of unwanted vegetation comprising applying to the locus wherevegetative control is desired a herbicidally-effective amount of abenzamide defined by the above general formula. The herbicidal method isideally carried out employing the preferred benzamides as delineatedabove. For example, a preferred method comprises applying to the locuswhere the growth of unwanted vegetation is to be eliminated or retardeda herbicidally effective amount of a benzamide of the formula ##STR18##wherein R² and R³ independently are C₁ -C₄ alkoxy such as methoxy orethoxy, and R⁴ is selected from ##STR19## wherein R⁵ is ##STR20## and R⁶and R⁷ independently are C₁ -C₄ alkyl and R⁸ is C₁ -C₁₃ alkyl orcycloalkyl of the formula ##STR21##

DETAILED DESCRIPTION OF THE INVENTION

The term "benzamide" when used herein shall include compounds of theabove formula wherein Z is oxygen and thiobenzamide compounds of theabove formula wherein Z is sulfur. Preferred compounds of the inventionare benzamides of the above formula wherein Z is oxygen.

R¹, R² and R³ are used in the above formula to define groups whichincude C₁ -C₄ alkyl, C₁ -C₄ alkoxy, C₁ -C₄ alkylthio, and halogen. Theterm "C₁ -C₄ alkyl" refers to both straight and branched chain alkylgroups such as methyl, ethyl, isopropyl and tert.-butyl. The term "C₁-C₄ alkoxy" refers to the same C₁ -C₄ alkyl groups which are linkedthrough an oxygen atom. Such groups include methoxy, n-propoxy, n-butoxyand the like. Typical "C₁ -C₄ alkylthio" groups include methylthio,ethylthio and isopropylthio. "Halogen" as used herein refers to fluoro,chloro, bromo and iodo. As noted above, preferred benzamides are thosewherein R¹ is hydrogen and R² and R³ are alkoxy, especially methoxy orethoxy attached at the 2 and 6-positions of the benzamide phenyl ring.

R⁴ in the above formula defines an aryl moiety such as isoxazolyl,thiadiazolyl, isothiazolyl, triazolyl, pyrazolyl, oxadiazolyl, andpyridazinyl. The R⁴ aryl substituents defined herein are represented bythe following general formulas ##STR22##

Preferred benzamides of the invention are those defined by the aboveformula wherein R⁴ is 3-isoxazolyl, 5-isoxazolyl, 1,3,4-thiadiazolyl or2-pyridazinyl.

The aryl moiety defined by R⁴ is required to bear a substituent definedby R⁵. It has been found that the most active, and accordingly the mostpreferred benzamides, are those wherein the aryl substituent defined byR⁵ is a sterically hindered or bulky group. The concept of a stericallyhindered or bulky group is known to those skilled in the art. Such termsinclude herein groups which are attached to the aryl ring through asecondary or tertiary carbon atom. Cyclic groups which are linkedthrough a secondary or tertiary carbon atom also are bulky groups, asare cyclic groups attached directly to the aryl moiety.

A typical R⁵ substituent which is preferred is a bulky alky group. Forexample, R⁵ represents an alkyl substituent when it refers to a group ofthe formula ##STR23## and R⁶ and R⁷ refer to hydrogen or C₁ -C₄ alkyland R⁸ is C₁ -C₁₃ alkyl. The most bulky alkyl groups clearly are thosewherein one or both of R⁶ and R⁷ independently are C₁ -C₄ alkyl, andbenzamides bearing such substituents are preferred. Typically preferredbulky alkyl groups thus include tert.-butyl, 1,1-dimethylpropyl,1,1-diethylpentyl, 1-ethyl-1-propylhexyl, 1-ethyl-1-methylpropyl,1,1-diethyloctyl, 1,1-diethylpropyl, 1-methyl-1-n-propylheptyl,1-ethyl-1-isopropyloctyl, and 1,1-di-n-propyldecyl.

Other bulky alkyl groups which can be utilized include1,2-dimethylbutyl, 1,2-dimethylheptyl, 2,2-dimethylpentyl,1-ethylheptyl, 2,2-diethylpropyl, 1,1-dimethyl-2,2-diethylbutyl,1,1,2,2-tetramethylhexyl, and 1-methyl-1-n-propyl-2-ethyloctyl.

The aryl substituent defined by R⁵ in the above formula can be any ofseveral bulky substituents other than a straight or branched chain alkylgroup, including cycloalkyl of the formula ##STR24## wherein R⁶ ishydrogen, C₁ -C₄ alkyl, C₂ -C₄ alkenyl, C₂ -C₄ alkynyl, C₁ -C₆ alkoxy,or C₁ -C₆ alkylthio; R⁹ and R¹⁰ independently are hydrogen, halogen, C₁-C₄ alkyl or C₂ -C₄ alkenyl; Q¹ and Q² independently are CH₂,--(CH₂)_(n) O-- or (CH₂)_(n) S--, where n is zero and 1; and y is aninteger from 0 to 4. Preferred such groups are those wherein R⁶ is C₁-C₄ alkyl. Typical examples of such groups include 1-methylcyclobutyl,1-ethylcyclopentyl, 1-n-propyl-2,2-dichlorocyclopropyl,1-methylcycloheptyl, 1-ethylcycloheptyl, 1-ethyl-2,3-dimethylcyclobutyl,1-n-propyl-2-allylcyclopentyl,1,2,2-trimethyl-3-(2-methyl-1-propenyl)cyclopropyl,2-methyl-1,3-dithian-2-yl, 5-ethyl-1,3-dithian-5-yl,2-propyl-1,3-dioxan-2-yl, 5-methyl-1,3-dioxan-5-yl,2-butyl-1,3-thioxan-2-yl, 5-ethyl-1,3-thioxan-5-yl and the like.

R⁵ also refers to haloalkyl groups, alkenyl groups, and alkynyl groups,for instance when R⁵ is --CR⁶ R⁷ R⁸ wherein R⁷ or R⁸ is halo-C₁ -C₁₃alkyl, C₂ -C₁₃ alkenyl or C₂ -C₁₃ alkynyl respectively. Haloalkyl groupsare C₁ -C₁₃ alkyl groups bearing one or more halo substituents. Examplesof such haloalkyl, alkenyl and alkynyl substituents as defined by R⁵include 1,1-dimethyl-3-chloropropyl, 1,2-diethyl-3-bromohexyl,1-ethyl-1-n-propyl-8-iodononyl, 1,1-di-n-propyl-4, -4-difluorobutyl,1-methyl-1-isopropyl-1,2-chlorododecyl, 1,1-dimethyl-3-butenyl,2,3-diethy 4-hexenyl, 1,1-diethy-2,2-dimethyl-5-hexenyl,1,1,2,2,3,3,-hexamethyl-9-decenyl, 1,1-dimethyl-4-hexynyl,1,2-diethyl-3-heptynyl, 1-iso-propyl-3-butynyl, and the like.

R⁵ in the above formula defining the benzamides of the inventionadditionally refers to CR⁶ R⁷ R⁸ wherein R⁷ or R⁸ can be C₁ -C₄alkoxy-C₁ -C₆ alkyl, C₂ -C₄ alkanoyloxy-C₁ -C₆ alkyl, or C₁ -C₄alkylthio-C₁ -C₆ alkyl. These terms refer to straight or branched carbonchains from one to six carbon atoms in length which bear a C₁ -C₄straight or branched carbon chain linked through oxygen or sulfur, or aC₂ -C₄ alkanoic acid residue such as acetoxy or butyroxy. Preferredalkoxyalkyl and alkylthioalkyl groups defined by R⁵ are those which aresterically hindered or bulky, for example those which include a branchedcarbon chain attached directly to the aryl group (i.e. where one or bothof R⁶ and R⁷ are alkyl). Such preferred groups include1,1-dimethyl-2-methoxyethyl, 1-ethyl-3-methylthiopropyl,1,1-diethyl-2-isopropoxyethyl, 1-n-propyl-3-tert.-butylthiopropyl and2-ethyl-3-methyl-3-n-butoxypropyl. Other typical groups of this classinclude 1-methyl-1-acetoxymethyl-4-propionoxybutyl,1-ethyl-1-(3-methylthiopropyl)-6-acetoxyhexyl,1-n-propyl-1-(6-ethoxyhexyl)-6-isobutoxyhexyl,1-ethyl-1-acetoxymethyl-3-ethylthiopropyl,1-methyl-1-propionoxymethyl-4-methoxybutyl, and1-(2-acetoxyethyl)-5-propoxypentyl.

R⁵ also defines an alkyl group which bears a phenylalkyl or phenylalkoxymoiety, or a cycloalkyl moiety. For example, R⁵ refers to the group--CR⁶ R⁷ R⁸ in which R⁷ or R⁸ can include phenylalkyl, phenylalkoxy,cycloalkyl and cycloalkylalkyl substituents defined by the formulas##STR25## wherein y, m, n, Q¹, Q², R⁹ and R¹⁰ are defined above.Examples of benzamide aryl substituents thus defined by R⁵ include1,1-dimethyl-2-phenoxyethyl, 1,1-diethyl-3-benzyloxypropyl,1,1-diethyl-2-phenylethyl, 1n-propyl-3-(2-chlorophenyl)butyl,1,1-dimethyl-2-cyclohexylethyl,1-ethyl-2-methyl-2-(3-allylcyclohexyl)ethyl,1,1-diethyl-2-(3-phenylpropoxy)ethyl,1-iso-propyl-4-(2,2-dichlorocyclopentyl)butyl,1-ethyl-1-benzyl-4-cyclohexylbutyl,1-methyl-1-phenoxy-3-(1,3-dioxan-2-yl)propyl,1-n-butyl-1-cyclobutylmethyl-2-cyclohexylethyl,1,1-dimethyl-3-(1,3-dithian-5-yl)propyl,1-ethyl-4-(1-oxa-3-thian-2-yl)butyl and related groups.

The benzamides of this invention are prepared by processes which arepresently known in the art or which are analogous to art-known syntheticmethods. A preferred method for preparing the compounds is by acylationof an aryl amine of the formula H₂ NR⁴ with an appropriately substitutedbenzoic acid derivative according to the folowing sequence: ##STR26##wherein R¹, R², R³ and R⁴ are as defined above, and L is a good leavinggroup, for example lower alkanoyloxy such as formyloxy or acetoxy,halide such as chloro, bromo or iodo, or an activated ester forminggroup such as pentachlorophenoxy or the like. A preferred good leavinggroup is halogen such as chloro or bromo.

The acylation reaction can be carried out by commingling the benzoicacid derivative with about an equimolar quantity of the aryl amine in amutual solvent such as tetrahydrofuran, diethyl ether, dichloromethane,dioxane, dimethylsulfoxide, dimethylformamide, benzene, toluene, and thelike. If desired, a base can be utilized in the acylation reaction toact as an acid scavenger. Commonly used bases include sodium carbonate,sodium hydride, potassium carbonate, sodium hydroxide, pyridine,triethylamine and related bases. The acylation generally issubstantially complete after about two to about ninety hours whencarried out at a temperature of about 20° to about 200° C., preferablyfrom about 30° to about 120° C. The product of the reaction, an N-arylbenzamide of the invention, can be isolated by simply removing thereaction solvent, for instance by evaporation under reduced pressure.The product can be further purified if needed by any of several routinemethods, including crystallization from solvents such as ethanol, ethylacetate, diethyl ether, toluene, or the like; chromatography over solidsupports such as silica or alumina, and related purification techniques.

An alternative method for preparing the N-aryl benzamides of thisinvention comprises the direct coupling of a substituted benzoic acidwith an aryl amine. Such coupling reaction necessitates the use of acoupling reagent, for example any of the type of coupling reagentscommonly employed in the synthesis of peptides. Examples of suchcoupling reagents include the carbodiimides such asN,N'-dicyclohexylcarbodiimide, N,N'-diisopropylcarbodiimide, orN,N'-diethylcarbodiimide; the imidazoles such as carbonylimidazole; aswell as reagents such as N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline(EEDQ). The direct coupling of a substituted benzoic acid and an arylamine is carried out by combining about equimolar quantities of thestarting materials in the presence of an equimolar quantity or slightexcess of coupling reagent. The reaction generally is carried out in anunreactive organic solvent such as dichloromethane or dimethylformamide,and usually is complete within about twenty-four hours when conducted ata temperature of about 0° to about 30° C. The benzamide product isreadily isolated and purified by standard procedures.

Thiobenzamides defined by the above general formula wherein Z is sulfurform another important group of compounds that are herbicidally activeand are a further embodiment of this invention. The thiobenzamides ofthe invention are preferably prepared by thiating the correspondingbenzamides according to the following scheme: ##STR27## Any of severalthiating agents can be employed in the thiation reaction, includingphosphorus pentasulfide. An especially preferred thiating agent isLawesson's Reagent, which is[2,4-bis(4-methoxyphenyl)-1,3-dithia-2,4-diphosphetane-2,4-disulfide.This thiating reagent and its general use are described in detail inTetrahedron Letters, 22, 4061 (1980). The thiation reaction ispreferably carried out by reacting approximately equimolar quantities ofa benzamide and Lawesson's Reagent in a mutual organic solvent such astoluene or dioxane. The reaction generally is complete within about twoto ten hours when carried out at a temperature of about 50° to about150° C. The thiobenzamide that is formed can be isolated and purified bynormal methods, including chromatography and the like.

A further embodiment of the present invention are the agronomicallyacceptable salts of the benzamides defined by the above general formula.Such salts may be particularly preferred when it is desired to increasethe water solubility of the benzamides, since the agronomicallyacceptable salts are in general highly soluble in water and similarpolar solvents. Typical salts provided herein are prepared by reactionof a benzamide with a strong base such as sodium hydride, lithiumhydride or potassium hydride, generally in a solvent such as diethylether or the like. Sodium salts are preferred salt forms for thebenzamides of this invention. All of the alkali metal salts areagronomically acceptable.

The preparation of the benzamides of this invention requires the use ofstarting materials which are either known or are readily preparable bymethods familiar to those in the art. Most of the substituted benzoicacids which are required are commercially available. The reactivederivatives of such benzoic acids are prepared by routine procedures.For example, a preferred synthetic method according to this inventionrequires the use of substituted benzoic acid halides or mixedanhydrides. The acid halides are prepared by reaction of a benzoic acidwith a halogenating agent such as oxalyl chloride, thionyl chloride,phosphorus trichloride or phosphorus tribromide.

The benzoic acid anhydrides which can be condensed with an amine to forma benzamide can be made by reacting a benzoic acid alkali metal salt,for example a sodium or potassium salt, with an acid halide such asbenzoyl chloride or acetyl bromide.

Benzoic acid derivatives which are commonly employed in the synthesis ofthe benzamides of this invention include the following:

2,6-dimethoxybenzoyl chloride;

2,6-dimethoxybenzoyl formic anhydride;

2,6-diethoxybenzoyl bromide;

2,6-di-n-propoxybenzoyl iodide;

2,6-di-isopropoxybenzoyl bromide;

2-methoxy-6-n-propoxybenzoyl chloride;

2-methoxy-3-ethoxybenzoyl bromide;

3-ethoxy-5-n-propoxybenzoyl acetic anhydride;

2,4,6-triethylbenzoyl bromide;

3,5-di-n-butylbenzoyl chloride;

2-methoxy-6-chlorobenzoyl bromide;

2,6-di-n-propoxybenzoyl acetic anhydride;

2-methoxy-6-fluorobenzoyl bromide;

2,6-dimethoxy-4-trifluoromethylbenzoyl chloride;

2,6-diethylbenzoyl iodide;

2,4,6-trimethoxybenzoyl chloride;

2-methoxy-6-ethylthiobenzoyl bromide;

2-methoxy-6-ethyl-4-trifluoromethyl benzoyl bromide, and the like.

The aryl amines of the formula H₂ NR⁴ which are required as startingmaterials are either readily available commercially or are preparable byart-recognized procedures. For example, 3-substituted-5-aminoisoxazolescan be prepared by reaction of a suitable carboxylic acid ester such asR⁵ COOCH₃ with acetonitrile and a strong base such as sodium hydride,followed by reaction with hydroxylamine according to the followingscheme: ##STR28## Similarly, 5-substituted-3-amino-isoxazoles can beprepared by iminoether formation with a suitably substitutedβ-ketonitrile followed by treatment with hydroxylamine to form animinium salt, and finally reaction with a protonic acid according to thefollowing general scheme: ##STR29##

The thiadiazole amines which are required as starting materials can beprepared by reaction of a carboxylic acid halide with thiosemicarbazideas follows: ##STR30## Similarly, pyrazole amines can be synthesized byreacting hydrazine with a suitably substituted β-keto nitrile accordingto the following scheme: ##STR31## Hydrazine is also utilized in thesynthesis of triazole derivatives according to the following path:##STR32##

Imidazolyl amines can be prepared by reacting cyanamide with anaminomethyl ketone according to the following scheme: ##STR33##Aminomethyl ketones also are reacted with ammonia, hydrogen sulfide andhydrogen peroxide to give amino isothiazoles: ##STR34##

Amino oxadiazoles are readily prepared by reaction of an amide oximewith trichloroacetic anhydride fokllowed by treatment with ammonia:##STR35##

Amino pyridazines are prepared by reaction of ammonia with a suitablysubstituted halopyridazine according to the following scheme: ##STR36##

These and other synthetic paths leading to aryl amines of the formula H₂NR⁴ are well known to those skilled in the art of organic chemistry.

As already pointed out, preferred aryl substituents defined in the abovegeneral formula by R⁴ include 3-isoxazolyl, 5-isoxazolyl and1,3,4-thiadiazol-2-yl. Typical examples of isoxazolyl amines andthiadiazolyl amines which are employed as starting materials to beacylated with a benzoic acid derivative include the following:

3-tert.-butyl-5-aminoisoxazole;

3-(1,1-dimethylpentyl)-5-aminoisoxazole;

3-(1,1-diethyl-4-ethoxybutyl)-5-aminoisoxazole;

3-(1-ethylcyclohexyl)-5-aminoisoxazole;

3-(1,2-diethyl-5-hexenyl)-5-aminoisoxazole;

3-(2,2-di-n-propyl-4-cycloheptylbutyl)-5-aminoisoxazole;

3-[1,1-dimethyl-3-(4-phenylbutoxy)propyl]-5-aminoisoxazole;

3-(1,1-diethyl-5-cyclohexylpentyl)-5-aminoisoxazole;

3-(1-n-butyl-2,3-dichlorocyclopropyl)-5-aminoisoxazole;

3-amino-5-(1,1-diethylheptyl)isoxazole;

3-amino-5-(1-isopropyl-3-cyclohexylpropyl)isoxazole;

3-amino-5-(1,1-dimethyl-6-heptenyl)isoxazole;

3-amino-5-[1,1-diethyl-3-(2,6-dibromophenyl)propyl]isoxazole;

3-amino-5-(1,1-di-n-propyl-6-iodohexyl)isoxazole;

3-amino-5-(1,2-dimethyl-3-ethylthiopropyl)isoxazole;

3-amino-5-(2,3-dimethyl-5-isobutoxypentyl)isoxazole;

3-amino-5-(1,4-dimethyl-2,2,3-triethyl-5-bromopentyl)isoxazole;

2-amino-5-tert.-butyl-1,3,4-thiadiazole;

2-amino-5-(1-ethyl-1-methylpropyl)-1,3,4-thiadiazole;

3-amino-4-methyl-5-(1,1-dimethylpropyl)isoxazole;

3-(methyl-1-methylthiomethyl-3-methoxypropyl)-4-n-butyl-5-aminoisoxazole;

3-amino-4-isobutyl-5-(2-ethyl-1,3-dioxan-2-yl)isoxazole;

2-amino-5-(1-methyl-1-methylthiomethyl-3-ethoxypropyl)-1,3,4-thiadiazole;

2-amino-5-(2-ethyl-1,3-dioxan-2-yl)-1,3,4-thiadiazole;

2-amino-5-(1,1-dimethyl-3-phenoxypropyl)-1,3,4-thiadiazole;

2-amino-5-(1,1-diethyl-5-ethylthiopentyl)-1,3,4-thiadiazole;

2-amino-5-[2,2-di-n-propyl-4-(2-methylphenoxy)butyl]-1,3,4-thiadiazole;

2-amino-5-(1-ethyl-3-isopropyl-4-chlorocyclopentyl)-1,3,4-thiadiazole;

2-amino-5-(2-n-propyl-3-methyl-5-tert.-butylthiopentyl)-1,3,4-thiadiazole;

2-amino-5-(1,1-dimethyl-3-iodopropyl)-1,3,4-thiadiazole;

2-amino-5-(1,1-di-n-propyldecyl)-1,3,4-thiadiazole;

2-amino-5-(1,1-diethyl-6-heptynyl)-1,3,4-thiadiazole;

Additional aryl amines which can be employed in the synthesis of thebenzamide herbicides of this invention include oxadiazoles, triazoles,isothiazoles, imidazoles, pyrazoles, and pyridazines. Illustrative ofthe such commonly used aryl amines are:

2-amino-5-(1-ethyl-1-methylpropyl)-1,3,4-oxadiazole;

2-amino-5-tert.-butyl-1,3,4--oxadiazole;

2-amino-5-(1,1-dimethyl-6-isopropoxyhexyl)-1,3,4-oxadiazole;

5-amino-3-(1-n-propylcycloheptyl)-1,2,4-oxadiazole;

3-amino-5-(1,1-dimethyl-3-ethyl-4-methylthiobutyl)-1,2,4-oxadiazole;

2-amino-5-[1,1-di-n-propyl-3-(4-bromophenyl)propyl]-1,3,4-oxadiazole;

2-amino-1,3,4-triazole;

5-amino-4-(1-ethyl-1-methylpropyl)-1,2,3-oxadiazole;

4-amino-5-(1-ethyl-1-cyclopropylmethyl-2-phenyl)-1,2,3-thiadiazole;

5-amine-4-(1-methyl-1-methoxymethyl-2-methylthioethyl)-1,2,3-triazole;

3-amino-5-tert.-butyl-1,2,4-triazole;

2-amino-5-(1,1-diethylhexyl)-1,3,4-triazole;

2-amino-5-(1-n-propyl-2,2-dibromocyclopropyl)-1,3,4-triazole;

3-amino-5-(1,1-diethyl-4-fluorobutyl)-1,2,4-triazole;

2-amino-5-(1,1-dimethyl-2,2-diethyl-3-n-propyl-4-pentenyl)-1,3,4-triazole;

3-amino-5-(1,1-diethylpropyl)-1,2,4-thiadiazole;

5-amino-3-[1-(2-butynyl)cyclohexyl]-1,2,4-oxadiazole;

5-amine-2-(1,1-dimethyl-3-chloropropyl)-1,3,4-oxadiazole;

3-amine-5-(1,1-diethylheptyl)-1,2,4-oxadiazole;

2-amino-5-(1-ethyl-1-methyl-6-n-butylthiohexyl)-1,3,4-triazole;

5-amino-3-(1,1-diethyl-2-methylhexyl)isothiazole;

5-amino-3-tert.-butylisothiazole;

5-amino-3-(1-n-propylcycloheptyl)isothiazole;

5-amino-3-[1,1-diethyl-4-(3-methylcyclopentyl)butyl]isothiazole;

3-amino-5-(1,1-diethylhexyl)isothiazole;

3-amino-5-[1-ethyl-2-methyl-4-(3-phenoxypropyl)octyl]isothiazole;

3-amino-5-(1,2,3-trimethyl-5-chloroheptyl)isothiazole;

3-amino-5-(1,1-diethyl-5-n-butylthiopentyl)isothiazole;

5-amino-3-(1,1-di-n-propylhexyl)pyrazole;

5-amino-3-tert.-butylpyrazole;

5- amino-3-(1-ethyl-1-methylpropyl)pyrazole;

5-amino-3-(1,1-diethyl-4-pentenyl)pyrazole;

5-amino-3-[1,1-dimethyl-4-(3-phenylpropoxy)butyl]pyrazole;

5-amino-3-(2,2-diethyldecyl)pyrazole;

3-amino-5-(1-ethyl-4,4-dimethyl-5-chloropentyl)pyrazole;

3-amino-5-(1-ethyl-1-methylpropyl)pyrazole;

3-amino-5-(1,1-dimethyl-6-n-butoxyphenyl)pyrazole;

2-amino-5-(1-ethyl-1-methylpropyl)-imidazole;

2-amino-5-[1-(2-propenyl)-1-(2-propynyl)-4-hexenyl]-imidazole;

2-amino-5-[1-ethyl-4-phenylbutyl)imidazole;

3-amino-5-(1,1-dibutylhexyl)pyrazole;

3-amino-5-(1,1-diethyl-4-cyclohexylbutyl)pyrazole;

3-amino-6-(1-ethyl-1-methylpropyl)pyridazine; and

3-amino-6-(1-ethylcyclohexyl)pyridazine.

A particularly preferred class of benzamides provided by this inventionis represented by the formula ##STR37## in which R⁴ is ##STR38## andwherein R⁵ is ##STR39## in which R⁶ is C₁ -C₄ alkyl, R⁷ is hydrogen orC₁ -C₄ alkyl, R⁸ is C₁ -C₁₃ alkyl and y is an integer from zero to four.

Among the most preferred compounds falling within this preferred classare:

N-[3-(1-ethyl-1-methylpropyl)-5-isoxazolyl]-2,6-dimethoxybenzamide;

N-[3-(tert.-butyl)-5-isoxazolyl]-2,6-dimethoxybenzamide;

N-[5-(1-ethyl-1-methylpropyl)-1,2,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide;

N-[5-(1,1-diethylpropyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide;

N-[3-(1,1-dimethylpropyl)-5-isoxazolyl]-2,6-dimethoxybenzamide;

N-[3-(1,1-diethylhexyl)-5-isoxazolyl]-2,6-dimethoxybenzamide;

N-[5-(1-ethylheptyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide;

N-[3-(1,1-diethylheptyl)-5-isoxazolyl]-2,6-dimethoxybenzamide;

N-[3-(1-ethyl-1-methylbutyl)-5-isoxazolyl]-2,6-dimethoxybenzamide;

N-[3-(1,1-diethylbutyl)-5-isoxazolyl]-2,6-dimethoxybenzamide;

N-[5-(1-methylbutyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide;

N-[5-(1-ethyl-1-methylhexyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide;

N-[3-(1,1-dimethyltetradecyl)-5-isoxazolyl]-2,6-dimethoxybenzamide;

N-[5-(1,2-dimethylbutyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide;

N-[5-(1,1-diethylhexyl)-3-isoxazolyl]-2,6-dimethoxybenzamide;

N-[5-(1,1,2-trimethylbutyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide;

N-[3-(1,1,2,2-tetramethylbutyl)-5-isoxazolyl]-2,6-dimethoxybenzamide;

N-[3-(1-ethylhexyl)-5-isoxazolyl]-2,6-dimethoxybenzamide;

N-[5-(1-ethyl-1-methylpentyl)-3-isoxazolyl]-2,6-dimethoxybenzamide;

N-[5-(1,1-diethyldecyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide;

N-5-(1-isopropylcyclohexyl)-3-isoxazolyl]-2,6-dimethoxybenzamide;

N-[5-(1-methylcyclopropyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide;

N-[5-(1-ethylcycloheptyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide;

N-[3-(1-isopropylcyclopentyl)-5-isoxazolyl]-2,6-dimethoxybenzamide;

Another especially preferred class of benzamides provided by thisinvention are those of the formula ##STR40## wherein R⁵ is ##STR41## inwhich R⁶ is C₁ -C₄ alkyl, R⁷ is hydrogen or C₁ -C₄ alkyl, R⁸ is C₁ -C₁₃alkyl, and y is an integer from zero to four.

Among the most preferred compounds falling within this preferred classare:

N-[6-(1-ethyl-1-methylpropyl)-pyridazin-3-yl]-2,6-dimethoxybenzamide;

N-[6-(1,1-dimethylethyl)-pyridazin-3-yl]-2,6-dimethoxybenzamide;

N-[6-(1-ethyl-1-methyldecyl)-pyridazin-3-yl]-2,6-dimethoxybenzamide;

N-[6-(1-n-butyloctyl)-pyridazin-3-yl]-2,6-dimethoxybenzamide;

N-[6-(1-methylethyl)-pyridazin-3-yl]-2,6-dimethoxybenzamide;

N-[6-(1-ethylcyclohexyl)-pyridazin-3-yl]-2,6-dimethoxybenzamide;

N-[6-(1-methylcyclobutyl)-pyradazin-3-yl]-2,6-dimethoxybenzamide;

Other specific compounds embraced by this invention include:

N-[5-(1,1-diethyl-2-methylthioethyl)-1,3,4-thiadiazol-2-yl]-2,6-diethoxybenzamide;

N-[5-(1-ethyl-1-methylpropyl)-1,2,3-thiadiazol-4-yl]-2,6-dimethoxybenzamide;

N-[5-(1-ethylcyclohexyl)-1,2,3-thiadiazol-4-yl]-2,6-dimethoxybenzamide;

N-[5-(2,2-diethylbutyl)-1,3,4-thiadiazol-2-yl]-2,6-diethoxybenzamide;

N-[5-(1,2-diethyl-3-isopropoxypropyl]-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide;

N-[3-(1,1-dimethyl-2-cycloheptylethyl)-5-isoxazolyl]-2,6-di-n-propoxybenzamide;

N-[3-(2,2-diethylhexyl)-5-isoxazolyl[-2,6-dimethoxybenzamide;

N-[5-(1,1-diethyl-2-phenylethyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide;

N-[3-(1,1-diethylhexyl)-5-isoxazolyl]-2,6-diethoxybenzamide;

N-[5-(1,1-diethyl-5-fluoropentyl]-1,3,4-thiadiazol-2-yl]-2,6-di-n-propoxybenzamide;

N-[3-(1,1-diethyl-2-methoxyethyl)-5-isoxazolyl]-2,6-dimethoxybenzamide;

N-[5-(1,1-diethylpentyl)-4H-1,2,4-triazol-3-yl)-2,6-methoxybenzamide;

N-[5-(1-ethyl-1-methylbutyl)-1,3,4-thiadiazol-2-yl]-2,6-diethylbenzamide;

N-[3-(1-ethyl-1-phenylethyl)-5-isoxazolyl]-2,6-diethoxybenzamide;

N-[5-(1-ethyl-1-methyl-3-chloropropyl)-1,3,4-thiadiazol-2-yl]-4-methoxybenzamide;

N-[5-(1-ethyl-1-methyl-3-methoxypropyl)-1,3,4-thiadiazol-2-yl]-2,4,6-triethoxybenzamide;

N-[3-(1-methyl-1-benzyloxyethyl)-5-isoxazolyl]-2,6-dimethoxybenzamide;

N-[3-(1,1-di-n-propyl-5-phenylpentyl)-5-isoxazolyl]-2,6-diethoxybenzamide;

N-[4-(1,1-diethylpentyl)-1,2,3-oxadiazol-5-yl]-2,6-dimethoxybenzamide;

N-[5-(1-ethyl-1-acetoxymethyl-3-methoxypropyl)-1,2,3-oxadiazol-4-yl]-2,6-dimethoxybenzamide;

N-[5-(1-ethyl-1-butylhexyl)-1,2,3-triazol-4-yl]-2,6-dimethoxybenzamide;

N-[4-(1-ethyl-2-phenoxyethyl)-1,2,3-triazol-5-yl]-2,6-dimethoxybenzamide;

N-[5-(1-ethylcyclobutyl)-1,3,4-thiadiazol-2-yl]-2,6-diethoxybenzamide;

N-[3-(1,1-diethyl-3-butenyl)-5-isoxazolyl]-2,6-diethoxybenzamide;

N-[5-(1-methylcyclopropyl)-1,3,4-thiadiazol-2-yl]-2,6-diethoxybenzamide;

N-[5-(1-ethylcycloheptyl)-1,3,4-thiadiazol-2-yl]-2,6-di-n-propoxybenzamide;

N-[3-(1,1-diethyl-5-chloropentyl)-5-isoxazolyl]-2,6-dimethoxybenzamide;

N-[3-(1-n-propylcyclobutyl)-5-isoxazolyl]-2,6-diethoxybenzamide;

N-[3-(1-isopropylcyclopentyl)-5-isoxazolyl]-2-ethylthio-6-methoxybenzamide;

N-[3-(2-methyl-3-(2-methyl-1-propenyl)cyclobutyl)-5-isoxazolyl]-2,6-diethoxybenzamide;

N-[5-(1,1-dimethyl-3-pentenyl)-1,3,4-thiadiazol-2-yl]-2-methoxy-6-n-propoxybenzamide;

N-[3-(1,1-dimethylpropyl)-1H-pyrazol-5-yl]-2,6-diethoxybenzamide;

N-[3-(1-ethyl-1-methylpropyl)-5-isoxazolyl]-2-fluoro-6-ethoxybenzamide;

N-[3-(1,1-di-n-propylpentyl)-1H-pyrazol-5-yl-2-methoxy-6-ethoxybenzamide;

N-[5-(1,1-dimethylpropyl)-1,3,4-thiadiazol-2-yl]benzamide;

N-[5-(1-ethylcyclopentyl)-1,3,4-thiadiazol-2-yl]-2,6-diethoxybenzamide;

N-[5-(1-methyl-1-n-propylpentyl)-1,3,4-thiadiazol-2-yl]-2-methyl-6-methylthiobenzamide;

N-[5-(1-ethylcycloheptyl)-4-ethyl-3-isoxazolyl]-2,6-dimethoxybenzamide;

N-[3-(1,1-dimethylheptyl)-4-methyl-5-isoxazolyl]-2,6-diethoxybenzamide;

N-[3-(1-ethyl-1-methylbutyl)-5-isoxazolyl]-2-bromo-6-methoxybenzamide;

N-[5-(1-ethyl-1-methyldecyl)-1,2,4-thiadiazol-2-yl]-2,6-dimethoxy-4-trifluoromethylbenzamide;

N-[3-(tert.-butyl)-5-isothiazolyl]-2,6-diethoxybenzamide;

N-[3-(1,1-diethylpentyl)-5-isoxazolyl]-2,4,6-trimethylbenzamide;

N-[3-(1,1-diethylhexyl)-5-isoxazolyl]-4-iodobenzamide;

N-[3-(1,2,2-trimethyl-1-ethylpropyl)-1,2,4-thiadiazol-5-yl]-3-ethylthio-6-methoxybenzamide;

N-[3-(1-ethyl-1-methylpropyl)-1,2,4-thiadiazol-5-yl]-2,6-di-n-propoxybenzamide;

N-[3-(1-ethyl-1-n-propylhexyl)-1,2,4-oxadiazol-5-yl]-2,6-diethoxybenzamide;

N-[3-(1-ethylcycloheptyl)-1,2,4-oxadiazol-5-yl]-2,4,5-trimethoxybenzamide;

N-[3-(1-ethyl-3-phenylpropyl)-1,2,4-oxadiazol-5-yl]-2,6-di(methylthio)benzamide;

N-[3-(1-methyl-1-ethyl-3-hexynyl)-1,2,4-oxadiazol-5-yl]-2,6-dimethoxybenzamide;

N-[5(4)-(1-ethyl-1-methylpropyl)-2-imidazolyl]-2,6-dimethoxybenzamide;

N-[5(4)-(1,1-dimethyl-5-phenylpentyl)-2-imidazolyl]-2,6-di(ethylthio)benzamide;

N-[5(4)-(2,2-diethyl-2-cyclobutylethyl)2-imidazolyl]-2,6-dimethoxy-4-(trifluoromethyl)benzamide;

N-[5(4)-(1-(3-butenyl)cyclohexyl)-2-imidazolyl]-2-chloro-4-methoxy-6-ethoxybenzamide;

N-[5-(1,1-dimethylpentyl)-4-ethyl-2-imidazolyl]-2,6-diethoxybenzamide;

N-[6-(1-methyl-1-acetoxymethyl-3-phenoxypropyl)-4-methyl-pyridazin-3-yl]-2,6-dimethoxybenzamide;

N-[6-(1-ethyl-1,3-dithian-2-yl)-5-isopropylpyridazin-3-yl]-2,6-dimethoxybenzamide;

N-[6-(1-methylcyclooctyl)pyridazin-3-yl]-2,6-dimethoxybenzamide;

N-[6-(5-ethyl-1,3-dioxan-5-yl)pyridazin-3-yl]-2,6-diethoxybenzamide;

N-[6-(1-ethyl-1-methylpropyl)pyridazin-3-yl]-2,6di-n-propoxybenzamide;

N-[6-(1-ethyl-3-cycloheptylpropyl)pyridazin-3-yl]-2,6-di-n-butoxybenzamide;and the like.

Thiobenzamides defined by the above general formula wherein Z is sulfuralso form an important class of compounds provided by this invention andare exemplified by the following:

N-[3-(1-ethyl-1-methylpropyl)-5-isoxazolyl]-2,6-dimethoxythiobenzamide;

N-[3-(tert.-butyl)-5-isoxazolyl]-2,6-dimethoxythiobenzamide;

N-[5-(1-ethyl-1-methylpropyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxythiobenzamide;

N-[5-(1,1-diethylpropyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxythiobenzamide;

N-[3-(1,1-dimethylpropyl)-5-isoxazolyl]-2,6-dimethoxythiobenzamide;

N-[3-(1,1-diethylhexyl)-5-isoxazolyl]-2,6-dimethoxythiobenzamide;

N-[5-(1-ethylheptyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxythiobenzamide;

N-[3-(1,1-diethylheptyl)-5-isoxazolyl]-2,6-dimethoxythiobenzamide;

N-[3-(1-ethyl-1-methylbutyl)-5-isoxazolyl]-2,6-dimethoxythiobenzamide;

N-[3-(1,1-diethylbutyl)-5-isoxazolyl]-2,6-dimethoxythiobenzamide;

N-[5-(1-methylbutyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxythiobenzamide;

N-[5-(1-ethyl-1-methylhexyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxythiobenzamide;

N-[3-(1,1-dimethyltetradecyl)-5-isoxazolyl]-2,6-dimethoxythiobenzamide;

N-[5-(1,2-dimethylbutyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxythiobenzamide;

N-[5-(1,1-diethylhexyl)-3-isoxazolyl]-2,6-dimethoxythiobenzamide;

N-[5-(1,1,2-trimethylbutyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxythiobenzamide;

N-[3-(1,1,2,2-tetramethylbutyl)-5-isoxazolyl]-2,6-dimethoxythiobenzamide;

N-[3-(1-ethylhexyl)-5-isoxazolyl]-2,6-dimethoxythiobenzamide;

N-[5-(1-ethyl-1-methylpentyl)-3-isoxazolyl]-2,6-dimethoxythiobenzamide;

N-[5-(1,1-diethyldecyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxythiobenzamide;

N-5-(1-isopropylcyclohexyl)-3-isoxazolyl]-2,6-dimethoxythiobenzamide;

N-[5-(1-methylcyclopropyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxythiobenzamide;

N-[5-(1-ethylcycloheptyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxythiobenzamide;

N-[3-(1-isopropylcyclopentyl)-5-isoxazolyl]-2,6-dimethoxythiobenzamide;

N-[5-(1,1-diethyl-2-methylthioethyl)-1,3,4-thiadiazol-2-yl]-2,6-diethoxythiobenzamide;

N-[6-(1-ethyl-1-methylpropyl)-pyridazin-3-yl]-2,6-dimethoxythiobenzamide;

N-[6-(1,1-dimethylethyl)-pyridazin-3-yl]-2,6-dimethoxythiobenzamide;

N-[6-(1-n-butyloctyl)-pyridazin-3-yl]-2,6-dimethoxythiobenzamide;

N-[6-(1-methylethyl)-pyridazin-3-yl]-2,6-dimethoxythiobenzamide;

N-[6-(1-ethylcyclobenzyl)-pyridazin-3-yl]-2,6-dimethoxythiobenzamide;

N-[6-(1-methylcyclobutyl)-pyradazin-3-yl]-2,6-dimethoxythiobenzamide;

N-[5-(2,2-diethylbutyl)-1,3,4-thiadiazol-2-yl]-2,6-diethoxythiobenzamide;

N-[5-(1,2-diethyl-3-isopropoxypropyl]-1,3,4-thiadiazol-2-yl]-2,6-dimethoxythiobenzamide;

N-[3-(1,1-dimethyl-2-cycloheptylethyl)-5-isoxazolyl]-2,6-di-n-propoxythiobenzamide;

N-[3-(2,2-diethylhexyl)-5-isoxazolyl]-2,6-dimethoxythiobenzamide;

N-[5-(1,1-diethyl-2-phenylethyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxythiobenzamide;

N-[3-(1,1-diethylhexyl)-5-isoxazolyl]-2,6-diethoxythiobenzamide;

N-[5-(1,1-diethyl-5-fluoropentyl]-1,3,4-thiadiazol-2-yl]-2,6-di-n-propoxythiobenzamide;

N-[3-(1,1-diethyl-2-methoxyethyl)-5-isoxazolyl]-2,6-dimethoxythiobenzamide;

N-[5-(1,1-diethylpentyl)-4H-1,2,4-triazol-3-yl)-2,6-dimethoxythiobenzamide;

N-[5-(1-ethyl-1-methylbutyl)-1,3,4-thiadiazol-2-yl]-2,6-diethylthiobenzamide;

N-[3-(1-ethyl-1-phenylethyl)-5-isoxazolyl]-2,6-diethoxythiobenzamide;

N-[5-(1-ethyl-1-methyl-3-chloropropyl)-1,3,4-thiadiazol-2-yl]-4-methoxythiobenzamide;

N-[5-(1-ethyl-1-methyl-3-methoxypropyl)-1,3,4-thiadiazol-2-yl]-2,4,6-triethoxythiobenzamide;

N-[3-(1-methyl-1-benzyloxyethyl)-5-isoxazolyl]-2,6-dimethoxythiobenzamide;

N-[3-(1,1-di-n-propyl-5-phenylpentyl)-5-isoxazolyl]-2,6-diethoxythiobenzamide;

N-[5-(1-ethylcyclobutyl)-1,3,4-thiadiazol-2-yl]-2,6-diethoxythiobenzamide;

N-[3-(1,1-diethyl-3-butenyl)-5-isoxazolyl]-2,6-diethoxythiobenzamide;

N-[5-(1-methylcyclopropyl)-1,3,4-thiadiazol-2-yl]-2,6-diethoxythiobenzamide;

N-[5-(1-ethylcycloheptyl)-1,3,4-thiadiazol-2-yl]-2,6-di-n-propoxythiobenzamide;

N-[3-(1,1-diethyl-5-chloropentyl)-5-isoxazolyl]-2,6-dimethoxythiobenzamide;

N-[3-(1-n-propylcyclobutyl)-5-isoxazolyl]-2,6-diethoxythiobenzamide;

N-[3-(1-isopropylcyclopentyl)-5-isoxazolyl]-2-ethylthio-6-methoxythiobenzamide;

N-[3-(2-methyl-3-(2-methyl-1-propenyl)cyclobutyl)-5-isoxazolyl]-2,6-diethoxythiobenzamide;

N-[5-(1,1-dimethyl-3-pentenyl)-1,3,4-thiadiazol-2-yl]-2-methoxy-6-n-propoxythiobenzamide;

N-[3-(1,1-dimethylpropyl)-1H-pyrazol-5-yl]-2,6-diethoxythiobenzamide;

N-[3-(1-ethyl-1-methylpropyl)-5-isoxazolyl]-2fluoro-6-ethoxythiobenzamide;

N-[3-(1,1-di-n-propylpentyl)-1H-pyrazol-5-yl-2-methoxy-6-ethoxythiobenzamide;

N-[5-(1,1-dimethylpropyl)-1,3,4-thiadiazol-2-yl]thiobenzamide;

N-[5-(1-ethylcyclopentyl)-1,3,4-thiadiazol-2-yl]-2,6-diethoxythiobenzamide;

N-[5-(1-methyl-1-n-propylpentyl)-1,3,4-thiadiazol-2-yl]-2-methyl-6-(methylthio)thiobenzamide;

N-[3-(1-ethyl-1-methylbutyl)-5-isoxazolyl]-2bromo-6-methoxythiobenzamide;

N-[5-(1-ethyl-1-methyldecyl)-1,2,4-thiadiazol-2-yl]-2,6-dimethoxy-4-trifluoromethylthiobenzamide;

N-[3-(tert.-butyl)-5-isothiazolyl]-2,6-diethoxybenzamide;

N-[3-(1,1-diethylpentyl)-5-isoxazolyl]-2,4,6-trimethylthiobenzamide;

N-[3-(1,1-diethylhexyl)-5-isoxazolyl]-4-iodothiobenzamide;

N-[3-(1,2,2-trimethyl-1-ethylpropyl)-1,2,4-thiadiazol-5-yl]-3-ethylthio-6-methoxythiobenzamide;

N-[3-(1-ethyl-1-methylpropyl)-1,2,4-thiadiazol-5-yl]-2,6-di-n-propoxythiobenzamide;

N-[3-(1-ethyl-1-n-propylhexyl)-1,2,4-oxadiazol-5-yl]-2,6-diethoxythiobenzamide;

N-[3-(1-ethylcycloheptyl)-1,2,4-oxadiazol-5-yl]-2,4,5-trimethoxythiobenzamide;

N-[3-(1-ethyl-3-phenylpropyl)-1,2,4-oxadiazol-5-yl]-2,6-di(methylthio)thiobenzamide;

N-[3-(1-methyl-1-ethyl-3-hexynyl)-1,2,4-oxadiazol-5-yl]-2,6-dimethoxythiobenzamide;

N-[5(4)-(1-ethyl-1-methylpropyl)-2-imidazolyl]-2,6-dimethoxythiobenzamide;

N-[5(4)-(1,1-dimethyl-5-phenylpentyl)-2-imidazolyl]-2,6-di(ethylthio)thiobenzamide;

N-[5(4)-(2,2-diethyl-2-cyclobutylethyl)2-imidazolyl]-2,6-dimethoxy-4-(trifluoromethyl)thiobenzamide;

N-[5-(4)-(1-(3-butenyl)cyclohexyl)-2-imidazolyl]-2-chloro-4-methoxy-6-ethoxythiobenzamide;

N-[6-(1-ethyl-1-methylpropyl)pyridazin-3-yl]-2,6-di-n-propoxythiobenzamide;

N-[6-(1-ethyl-3-cycloheptylpropyl)pyridazin-3-yl]-2,6-di-n-butoxythiobenzamide;and the like.

The preparation of various benzamides provided by the invention isillustrated by the following detailed examples. The exemplification isnot exhaustive of the compounds embraced by the invention nor of thepossible synthetic routes, and should not be so construed.

EXAMPLE 1N-[3-(1-Ethyl-1-methylpropyl)-5-isoxazolyl]-2,6-dimethoxybenzamide (A)Preparation of 5-amino-3-(1-ethyl-1-methylpropyl)isoxazole

A 16.5 Kg portion of methyl 2-ethylbutyrate was reacted with 60 Kg ofn-butyl lithium, diisopropylamine, and 19.1 Kg of methyl iodide toprovide 17.4 Kg of methyl 2-ethyl-2-methylbutyrate. A 7.5 Kg portion ofthe ester thus formed was reacted with 3.25 Kg of acetonitrile and 5.03g of sodium hydride in 33 liters of tetrahydrofuran to provide1-ethyl-1-methylpropyl cyanomethyl ketone. The ketone thus formed wasreacted with 4.35 Kg of hydroxylamine hydrochloride and 2.54 Kg ofsodium hydroxide in 44 liters of water to provide 5.65 Kg of5-amino-3-(1-ethyl-1-methylpropyl)isoxazole.

(B) Preparation of 2,6-dimethoxybenzoyl chloride

A 8.5 Kg portion of 2,6-dimethoxybenzoic acid was dissolved in 60 litersof toluene and the solution was stirred at ambient temperature while 6.8liters of thionyl chloride was added dropwise over forty-five minutes.Following the addition, the reaction mixture next was cooled to roomtemperature and the solvent was removed by evaporation under reducedpressure, washed with 25 liters of Pet. ether cooled and filtered toprovide a crude solid product. The product was stirred for one hour with25 liters of fresh Pet. ether, and then cooled to 10° C. and filtered toprovide 8.94 Kg of 2,6-dimethoxybenzoyl chloride.

(C) Synthesis ofN-[3-(1-ethyl-1-methylpropyl)-5-isoxazolyl]-2,6-dimethoxybenzamide

To a stirred solution of 3.36 Kg of5-amino-3-(1-ethyl-1-methylpropyl)isoxazole in 65 liters of toluene wasadded portion-wise over thirty minutes 4.015 Kg of 2,6-dimethoxybenzoylchloride. The reaction mixture was heated to reflux and stirred forforty-eight hours. It was then cooled to room temperature andconcentrated to a volume of about 25 liters by evaporation of thesolvent under reduced pressure. The product precipitated and wascollected by filtration, washed with fresh toluene, and air dried toprovide 6.084 Kg ofN-[3-(1-ethyl-1-methylpropyl]-5-isoxazolyl]-2,6-dimethoxybenzamide. M.P.172°-174° C. Yield 91%.

Analysis calculated for C₁₈ H₂₄ N₂ O₄ : Theory: C, 65.04; H, 7.28; N,8.43. Found: C, 64.79; H, 7.02; N, 8.28.

EXAMPLE 2N-[3-(1,1-dimethylethyl)-5-isoxazolyl]-2,6-di-n-propoxybenzamide (A)Preparation of 2,6-di-n-propoxybenzoyl chloride

Methyl 2,6-dihydroxybenzoate was reacted with n-propyl iodide in thepresence of sodium hydride to provide methyl 2,6-di-n-propoxybenzoate.The ester thus formed was saponified by reaction with 40% aqueouspotassium hydroxide in ethanol to afford 2,6-di-n-propoxybenzoic acid. A20 g portion of the acid was then reacted with 30 g of thionyl chloridein 100 ml of benzene at reflux for five hours. Removal of the solvent byevaportion under reduced pressure and purification of the product bydistillation provided 4.88 g of 2,6-di-n-propoxybenzoyl chloride. B.P.135°-140° C. at 0.2 torr.

(B)

To a stirred solution of 2.8 g of 5-amino-3-(1,1-dimethylethyl)isoxazolein 40 ml of tetrahydrofuran containing 4.5 ml of triethylamine was addeddropwise over ten minutes a solution of 4.88 g of2,6-di-n-propoxybenzoyl chloride in 10 ml of tetrahydrofuran. Followingthe addition, the reaction mixture was heated at reflux for seventy-twohours. The reaction mixture was then cooled to room temperature and thesolvent was removed by evaporation under reduced pressure. The residuewas dissolved in a mixture of dichloromethane and water, and the organiclayer was separated, washed with fresh water, dried, and the solvent wasremoved by evaporation to provide an oil. The oil was crystallized fromSkelly B and diethyl ether to provide 750 mg ofN-[3-(1,1-dimethylethyl)-5-isoxazolyl]-2,6-di-n-propoxybenzamide. M.P.85°-87° C. Yield 10%.

Analysis calculated for C₂₀ H₂₈ N₂ O₄ : Theory: C, 66.64; H, 7.83; N,7.77. Found: C, 67.65; H, 7.78; N, 7.32.

EXAMPLE 3 N-[5-(1-ethylcyclohexyl)-3-isoxazolyl]-2,6 -dimethoxybenzamide(A) Preparation of 3-amino-5-(1-ethylcyclohexyl)isoxazole

Acetonitrile was reacted with 1-ethyl-1-methyoxycarbonylcyclohexane inthe presence of sodium hydride to provide1-ethyl-1-(2-cyanoacetyl)cyclohexane. A 55 g portion of the lattercompound was dissolved in 200 ml of diethyl ether containing 20.5 g ofabsolute methanol, and the solution was stirred and cooled to about 5°C. Hydrogen chloride gas was next bubbled through the reaction mixturefor forty-five minutes, after which time the reaction mixture was storedat 0° C. for twelve hours. Removal of the reaction solvent byevaporation under reduced pressure provided a yellow solid, which wasdissolved in 300 ml of fresh absolute methanol and treated with 97 g oftriethylamine and 22 g of hydroxylamine hydrochloride. The reactionmixture was heated at 50° C. for three hours, and then cooled to roomtemperature and diluted with 25 ml of concentrated hydrochloric acid.The acidic reaction mixture was heated at 50° C. for twelve hours, andthen cooled to room temperature and concentrated to dryness byevaporation of the solvent under reduced pressure. The residue thusobtained was dissolved in water, and the aqueous mixture was madealkaline by the addition of 20% sodium hydroxide. The product wasextracted into diethyl ether, which was then washed with water, dried,and the solvent was removed by evaporation. Distillation of the productafforded 14 g of 3-amino-5-(1-ethylcyclohexyl)isoxazole. B.P. 135°-140°C. at 0.1-0.05 torr.

(B) A solution of 14 g of 3-amino-5-(1-ethylcyclohexyl)isoxazole and14.4 g of 2,6-dimethoxybenzoyl chloride in 100 ml of toluene was heatedto reflux and stirred for eighteen hours. The reaction mixture then wascooled to room temperature and the solvent was removed by evaporationunder reduced pressure to provide a solid. The solid was dissolved in200 ml of dichloromethane, washed with dilute sodium hydroxide and withbrine, dried, and the solvent was removed by evaporation. The productwas crystallized from dichloromethane and diethyl ether to provide 15.5g of N-[5-(1-ethylcyclohexyl)-3-isoxazolyl]-2,6-dimethoxybenzamide. M.P.179°-181° C. Yield 60%.

Analysis calculated for C₂₀ H₂₆ N₂ O₄ : Theory: C, 67.02; H, 7.31; N,7.82. Found: C, 66.81; H, 7.02; N, 7.54.

The following exemplary compounds were prepared by reacting anamino-isoxazole with a 2,6-dialkoxy benzoyl halide derivative accordingto the general methods of Examples 1-3 to provide the correspondingN-isoxazolyl-2,6-dialkoxybenzamide.

EXAMPLE 4N-[3-(1,1-dimethyl-2-chloroethyl)-5-isoxazolyl]-2,6-dimethoxybenzamide

M.P. 172°-173° C. Yield 33%.

Analysis calculated for C₁₆ H₁₉ ClN₂ O₄ : Theory: C, 56.72; H, 5.65; N,8.27; Cl, 10.46. Found: C, 56.49; H, 5.66; N, 8.08; Cl, 10.52.

EXAMPLE 5 N-[3-(2,2-dimethylpropyl)-5-isoxazolyl]-2,6-dimethoxybenzamide

M.P. 152°-154° C. Yield 24%.

Analysis calculated for C₁₇ H₂₂ N₂ O₄ : Theory: C, 64.13; H, 6.97; N,8.80. Found: C, 64.07; H, 6.76; N, 8.62.

EXAMPLE 6 N-[3-(1,1-dimethylethyl)-5-isoxazolyl]-2,6-dimethoxybenzamide

M.P. 172°-173° C. Yield 66%.

Analysis calculated for C₁₆ H₂₀ N₂ O₄ : Theory: C, 63.14; H, 6.62; N,9.20. Found: C, 62.90; H, 6.52; N, 8.94.

EXAMPLE 7 N-[5-(1,1-dimethylethyl)-3-isoxazolyl]-2,6-dimethoxybenzamide

M.P. 182°-183° C. Yield 27%.

Analysis calculated for C₁₆ H₂₀ N₂ O₄ : Theory: C, 63.14; H, 6.62; N,9.20. Found: C, 63.14; H, 6.64; N, 9.07.

EXAMPLE 8N-[3-(1,1-dimethylethyl)-5-isoxazolyl]-2-methoxy-6-isopropoxybenzamide

M.P. 126°-128° C. Yield 3.5%.

Analysis calculated for C₁₈ H₂₄ N₂ O₄ : Theory: C, 65.24; H, 7.00; N,8.45. Found: C, 65.00; H, 6.80; N, 8.39.

EXAMPLE 9 N-[3-(1,1-dimethylpropyl)-5-isoxazolyl]-2,6-dimethoxybenzamide

M.P. 140°-142° C. Yield 50%.

Analyis calculated for C₁₇ H₂₂ N₂ O₄ : Theory: C, 64.13; H, 6.97; N,8.80. Found: C, 63.86; H, 6.71; N, 9.05.

EXAMPLE 10N-[3-(1,1-dimethylpentyl)-5-isoxazolyl]-2,6-dimethoxybenzamide

M.P. 132°-133° C. Yield 31%.

Analysis calculated for C₁₉ H₂₆ N₂ O₄ : Theory: C, 65.88; H, 7.57; N,8.09. Found: C, 65.88; H, 7.42; N, 7.86.

EXAMPLE 11N-[3-(2-cyclohexyl-1,1-dimethylethyl)-5-isoxazolyl]-2,6-dimethoxybenzamide

M.P. 146°-148° C. Yield 21%.

Analysis calculated for C₂₂ H₃₀ N₂ O₄ : Theory: C, 68.37; H, 7.82; N,7.25. Found: C, 68.12; H, 7.57; N, 6.99.

EXAMPLE 12N-[3-(1-cyclohexyl-1-methylethyl)-5-isoxazolyl]-2,6-dimethoxybenzamide

M.P. 158°-160° C. Yield 91%.

Analysis calculated for C₂₁ H₂₈ N₂ O₄ : Theory: C, 67.72; H, 7.58; N,7.52. Found: C, 67.56; H, 7.37; N, 7.56.

EXAMPLE 13N-[3-(1,1-dimethyl-2-phenylethyl)-5-isoxazolyl]-2,6-dimethoxybenzamide

M.P. 108°-110° C. Yield 9%.

Analysis calculated for C₂₂ H₂₅ N₂ O₄ : Theory: C, 69.46; H, 6.36; N,7.36. Found: C, 69.28; H, 6.53; N, 7.12.

EXAMPLE 14N-[3-(1ethyl-1-methylbutyl)-5-isoxazolyl]-2,6-dimethoxybenzamide

M.P. 149°-151° C. Yield 41%.

Analysis calculated for C₁₉ H₂₆ N₂ O₄ : Theory: C, 65.88; H, 7.57; N,8.09. Found: C, 65.59; H, 7.35; N, 7.87.

EXAMPLE 15 N-[3-(1,1-diethylpropyl)-5-isoxazolyl]-2,6-dimethoxybenzamide

M.P. 163°-165° C. Yield 13%.

EXAMPLE 16N-[3-(1,1-dimethyl-3-butenyl)-5-isoxazolyl]-2,6-dimethoxybenzamide

M.P. 160°-162° C. Yield 22%.

Analysis calculated for C₁₈ H₂₂ N₂ O₄ ; Theory: C, 65.44; H, 6.71; N,8.48. Found: C, 65.23; H, 6.50; N, 8.39.

EXAMPLE 17N-[3-(1-methylcyclohexyl)-5-isoxazolyl]-2,6-dimethoxybenzamide

M.P. 161°-163° C. Yield 54%.

Analysis calculated for C₁₉ H₂₄ N₂ O₄ ; Theory: C, 66.26; H, 7.02; N,8.13. Found: C, 66.06; H, 6.80; N, 8.28.

EXAMPLE 18N-[3-(1,1-dimethyltetradecyl)-5-isoxazolyl]-2,6-dimethoxybenzamide

M.P. 57°-59° C. Yield 9%.

Analysis calculated for C₂₈ H₄₄ N₂ O₄ ; Theory: C, 71.15; H, 9.38; N,5.93. Found: C, 71.34; H, 9.15; N, 5.81.

EXAMPLE 19 N-[3-(1-ethylcyclohexyl)-5-isoxazolyl]-2,6-dimethoxybenzamide

M.P. 177°-179° C. Yield 34%.

Analysis calculated for C₂₀ H₂₆ N₂ O₄ ; Theory: C, 67.02; H, 7.31, N,7.82. Found: C, 66.74; H, 7.07; N, 7.90.

EXAMPLE 20N-[3-(1,1,3-trimethylbutyl)-5-isoxazolyl]-2,6-dimethoxybenzamide

M.P. 146°-148° C. Yield 12%.

Analysis calculated for C₁₉ H₂₆ N₂ O₄ ; Theory: C, 65.88; H, 7.57; N,8.09. Found: C, 65.70; H, 7.50; N, 7.87.

EXAMPLE 21N-[3-(1-methylcyclopentyl)-5-isoxazolyl]-2,6-dimethoxybenzamide

M.P. 128°-130° C. Yield 10%.

Analysis calculated for C₁₈ H₂₂ N₂ O₄ ; Theory: C, 65.44; H, 6.71; N,8.48. Found: C, 65.24; H, 6.59; N, 8.22.

EXAMPLE 22 N-[5-(1,1-dimethylbutyl)-3-isoxazolyl]-2,6-dimethoxybenzamide

M.P. 133°-135° C. Yield 48%.

Analysis calculated for C₁₈ H₂₄ N₂ O₄ ; Theory: C, 65.04; H, 7.28; N,8.43. Found: C, 65.25; H, 7.01; N, 8.19.

EXAMPLE 23N-[3-(1,1,2,2-tetramethylpropyl)-5-isoxazolyl]-2,6-dimethoxybenzamide

M.P. 174°-175° C.

Analysis calculated for C₁₉ H₂₆ N₂ O₄ ; Theory: C, 65.88; H, 7.57; N,8.09. Found: C, 65.97; H, 7.32; N, 8.33.

EXAMPLE 24 N-[3-(1-ethylpropyl)-5-isoxazolyl]-2,6-dimethoxybenzamide

M.P. 157°-159° C. Yield 53%.

Analysis calculated for C₁₇ H₂₂ N₂ O₄ ; Theory: C, 64.13; H, 6.97; N,8.80. Found: C, 63.87; H, 6.77; N, 8.56.

EXAMPLE 25N-[5-(1-ethyl-1-methylpropyl)-3-isoxazolyl]-2,6-dimethoxybenzamide

M.P. 165°-166° C. Yield 49%.

Analysis calculated for C₁₈ H₂₄ N₂ O₄ ; Theory: C, 65.04; H, 7.28; N,8.43. Found: C, 64.94; H, 7.01; N, 8.21.

EXAMPLE 26 N-[3-(1,1-dimethylethyl)-5-isoxazolyl]-2,6-dimethoxybenzamide

M.P. 123°-125° C. Yield 11%.

Analysis calculated for C₁₈ H₂₄ N₂ O₄ ; Theory: C, 65.04; H, 7.28; N,8.43. Found: C, 64.50; H, 7.04; N, 7.89.

EXAMPLE 27N-[3-(2-methoxy-1,1-dimethylethyl)-5-isoxazolyl]-2,6-dimethoxybenzamide

M.P. 201°-203° C. Yield 19%.

Analysis calculated for C₁₇ H₂₂ N₂ O₅ ; Theory: C, 61.06; H, 6.63; N,8.38. Found: C, 61.50; H, 6.36, N, 8.51.

EXAMPLE 28 N-[3-(1,1-dimethylbutyl)-5-isoxazolyl]-2,6-dimethoxybenzamide

M.P. 141°-143° C. Yield 9%.

Analysis calculated for C₁₈ H₂₄ N₂ O₄ ; Theory: C, 65.04; H, 7.28; N,8.43. Found: C, 64.79; H, 7.04; N, 8.26.

EXAMPLE 29N-[3-(1-propylcyclohexyl)-5-isoxazolyl]-2,6-dimethoxybenzamide

M.P. 202°-204° C. Yield 38%.

Analysis calculated for C₂₁ H₂₈ N₂ O₄ ; Theory: C, 67.72; H, 7.58; N,7.52. Found: C, 67.48; H, 7.58; N, 7.56.

EXAMPLE 30N-[3-(1-methyl-1-(2,4-dichlorophenoxy)ethyl)-5-isoxazolyl]-2,6-dimethoxybenzamide

M.P. 154°-156° C. Yield 25%.

Analysis calculated for C₂₁ H₂₀ Cl₂ N₂ O₅ ; Theory: C, 55,89; H, 4.47;N, 6.21; Cl, 15.71. Found: C, 56.09; H, 4.46; N, 6.01; Cl, 15.45.

EXAMPLE 31N-[3-(1-methyl-1-phenylethyl)-5-isoxazolyl]-2,6-dimethoxybenzamide

M.P. 185°-187° C. Yield 30%.

Analysis calculated for C₂₁ H₂₂ N₂ O₄ ; Theory: C, 68.84; H, 6.05; N,7.65. Found: C, 69.04; H, 5.93; N, 7.44.

EXAMPLE 32N-[3-(1-methyl-1-phenylpropyl)-5-isoxazolyl]-2,6-dimethoxybenzamide

M.P. 183°-185° C. Yield 29%.

Analysis calculated for C₂₂ H₂₄ N₂ O₄ ; Theory: C, 69.46; H, 6.36; N,7.36. Found: C, 69.26; H, 6.13; N, 7.54.

EXAMPLE 33N-[3-(1-methyl-1-(phenylmethoxy)ethyl]-5-isoxazolyl-2,6-dimethoxybenzamide

M.P. 123°-125° C. Yield 13%.

Analysis calculated for C₂₂ H₂₄ N₂ O₅ ; Theory: C, 66.65; H, 6.10; N,7.07. Found: C, 66.84; H, 5.88; N, 6.86.

EXAMPLE 34N-[3-(1-ethylcycloheptyl)-5-isoxazolyl]-2,6-dimethoxybenzamide

M.P. 163°-165° C. Yield 32%.

Analysis calculated for C₂₁ H₂₈ N₂ O₄ ; Theory: C, 67.72; H, 7.58; N,7.52. Found: C, 67.64; H, 7.78; N, 7.25.

EXAMPLE 35N-[3-(1-cyclohexyl-1-methylpropyl)-5-isoxazolyl]-2,6-dimethoxybenzamide

M.P. 173°-175° C. Yield 22%.

Analysis calculated for C₂₂ H₃₀ N₂ N₄ ; Theory: C, 68.37; H, 7.82; N,7.25. Found: C, 68.29; H, 7.53; N, 7.27.

EXAMPLE 36N-[3-(1-methoxy-1-methylethyl)-5-isoxazolyl]-2,6-dimethoxybenzamide

M.P. 232°-234° C. Yield 37%.

Analysis calculated for C₁₆ H₂₀ N₂ O₅ ; Theory: C, 59.99; H, 6.29; N,8.74. Found: C, 59.87; H, 6.07; N, 8.73.

By the following the general procedures of Examples 1-3, anamino-isoxazole was reacted with a suitably substituted benzoyl halideto give the following N-isoxazolyl benzamides.

EXAMPLE 37N-[3-(1-ethyl-1-methylpropyl)-5-isoxazolyl]2fluoro-6-methoxybenzamide

M.P. 133°-135° C. Yield 26%.

Analysis calculated for C₁₇ H₂₁ N₂ O₃ F; Theory: C, 63.74; H, 6.61; N,8.74. Found: C, 63.97; H, 6.48; N, 8.70.

EXAMPLE 38 N-[5-(1,1-dimethylethyl)-3-isoxazolyl]-2,6-dichlorobenzamide

M.P. 249°-250° C.

Analysis calculated for C₁₄ H₁₄ Cl₂ N₂ O₂ ; Theory: C, 53.69; H, 4.51;N, 8.94. Found: C, 53.89; H, 4.54; N, 8.77.

EXAMPLE 39 N-[3-(1,1-dimethylethyl)-5-isoxazolyl]-2,6-dichlorobenzamide

M.P. 235°-237° C. Yield 22%.

Analysis calculated for C₁₄ H₁₄ Cl₂ N₂ O₂ ; Theory: C, 53.69; H, 4.51;N, 8.94; Cl, 22.64. Found: C, 53.74; H, 4.56; N, 8.96; Cl, 22.83.

EXAMPLE 40 N-[3-(1,1-dimethylethyl)-5-isoxazolyl]-2,6-difluorobenzamide

M.P. 153°-154° C.

Analysis calculated for C₁₄ H₁₄ F₂ N₂ O₂ ; Theory: C, 60.00; H, 5.04; N,10.00. Found: C, 59.91; H, 4.83; N, 10.16.

EXAMPLE 41N-[3-(1-ethyl-1-methylpropyl)-5-isoxazolyl]-2-chloro-6-methoxybenzamide

M.P. 173°-174° C. Yield 42%.

Analysis calculated for C₁₇ H₂₁ ClN₂ O₃ ; Theory: C, 60.62; H, 6.28; N,8.32. Found: C, 6.74; H, 6.02; N, 8.54.

EXAMPLE 42N-[3-(1-ethyl-1-methylpropyl)-5-isoxazolyl]-2,4,6-trimethoxybenzamide

M.P. 150°-152° C. Yield 40%.

Analysis calculated for C₁₉ H₂₆ N₂ O₅ ; Theory: C, 62.97; H, 7.23; N,7.73. Found: C, 63.01; H, 7.05; N, 7.72.

EXAMPLE 43N-[5-(1-ethyl-1-methylpropyl)-3-isoxazolyl]-2,4,6-trimethoxybenzamide

M.P. 165°-170° C. Yield 41%.

Analysis calculated for C₁₉ H₂₆ N₂ O₅ ; Theory: C, 62.97; H, 7.23; N,7.73. Found: C, 62.94; H, 6.99; N, 7.94.

EXAMPLE 44N-[3-(1-ethyl-1-methoxymethylpropyl)-5-isoxazolyl]-2,6-dimethoxybenzamideEXAMPLE 45N-[3-(1,1-diethyl-2-propenyl)-5-isoxazolyl]-2,6-dimethoxybenzamideEXAMPLE 46 N-[3-(1,1-dimethylethyl)-5-isoxazolyl]-2,4-dimethoxybenzamide

M.P. 166°-168° C. Yield 53%.

Analysis calculated for C₁₆ H₂₀ N₂ O₄ ; Theory: C, 63.14; H, 6.62; N,9.20. Found: C, 63.38; H, 6.71; N, 9.01.

EXAMPLE 47 N-[3-(1,1-dimethylethyl)-5-isoxazolyl]-3,5-dimethylbenzamide

M.P. 121°-123° C. Yield 45%.

Analysis calculated for C₁₆ H₂₀ N₂ O₂ ; Theory: C, 70.56; H, 7.40; N,10.29. Found: C, 70.82; H, 7.25; N, 10.21.

EXAMPLE 48 N-[3-propyl-5-isoxazolyl]-2,6-dimethoxybenzamide

M.P. 124°-126° C. Yield 29%.

Analysis calculated for C₁₅ H₁₈ N₂ O₄ ; Theory: C, 62.06; H, 6.25; N,9.65. Found: C, 62.34; H, 6.46; N, 9.55.

EXAMPLE 49 N-(3-propyl-5-isoxazolyl)-2,6-dimethylbenzamide

M.P. 120°-122° C.

Analysis calculated for C₁₅ H₁₈ N₂ O₂ ; Theory: C, 69.74; H, 7.02; N,10.84. Found: C, 69.98; H, 6.82; N, 10.58.

EXAMPLE 50 N-[3-(1,1-dimethylethyl)-5-isoxazolyl]-3,4-dimethoxybenzamide

M.P. 164°-166° C. Yield 37%.

Analysis calculated for C₁₆ H₂₀ N₂ O₄ ; Theory: C, 63.14; H, 6.62; N,9.20. Found: C, 63.27; H, 6.41; N, 9.12.

EXAMPLE 51 N-[3-(1,1-dimethylethyl)-5-isoxazolyl]-3,5-dimethoxybenzamide

M.P. 115°-117° C. Yield 49%.

Analysis calculated for C₁₆ H₂₀ N₂ O₄ ; Theory: C, 63.14; H, 6.62; N,9.20. Found: C, 63.40; H, 6.37; N, 9.30.

EXAMPLE 52 N-[3-(1-methylethyl)-5-isoxazolyl]-2,6-dimethoxybenzamide

M.P. 143°-144° C. Yield 52%.

Analysis calculated for C₁₅ H₁₈ N₂ O₄ ; Theory: C, 62.49; H, 5.59; N,9.72. Found: C, 62.20; H, 5.46; N, 9.51.

EXAMPLE 53N-[3-(1,1-dimethylethyl)-5-isoxazolyl]-2,4,6-trimethylbenzamide

M.P. 177°-179° C. Yield 22%.

Analysis calculated for C₁₇ H₂₂ N₂ O₂ ; Theory: C, 71.30; H, 7.74; N,9.78. Found: C, 71.34; H, 7.45; N, 9.78.

EXAMPLE 54N-[3-(1-ethyl-1-(methoxymethyl)propyl)-5-isoxazolyl]-2,6-dimethoxybenzamide

M.P. 167°-168° C. Yield 26%.

Analysis calculated for C₁₉ H₂₆ N₂ O₅ ; Theory: C, 62.97; H, 7.23; N,7.73. Found: C, 63.23; H, 7.00; N, 7.76.

EXAMPLE 55N-[3-(1-ethyl-1-methylpentyl)-5-isoxazolyl]-2,6-dimethoxybenzamide

M.P. 150°-152° C. Yield 34%.

Analysis calculated for C₂₁ H₃₀ N₂ O₄ ; Theory: C, 66.54; H, 7.83; N,7.77. Found: C, 66.76; H, 7.67; N, 7.53.

EXAMPLE 56 N-[3-(1,1-dimethylethyl)-5-isoxazolyl]-2,6-dimethylbenzamide

M.P. 179°-181° C. Yield 32%.

Analysis calculated for C₁₆ H₂₀ N₂ O₂ ; Theory: C, 70.56; H, 7.40; N,10.29. Found: C, 70.35; H, 7.19; N, 10.02.

EXAMPLE 57N-[3-(2,2-dimethyl-3-[2-methyl-1-propenyl]cyclopropyl)-5-isoxazolyl]-2,6-dimethoxybenzamide

M.P. 92°-94° C. Yield 8%.

Analysis calculated for C₂₁ H₂₄ N₂ O₄ ; Theory: C, 68.09; H, 7.07; N,7.56. Found: C, 68.16; H, 6.83; N, 7.42.

EXAMPLE 58N-[3-(1-ethyl-1-methoxypropyl)-5-isoxazolyl]2,6-dimethoxybenzamide

M.P. 174°-176° C. Yield 7%.

Analysis calculated for C₁₈ H₂₄ N₂ O₅ ; Theory: C, 62.05; H, 6.44; N,8.04. Found: C, 61.83; H, 6.87; N, 7.82.

EXAMPLE 59 N-[3-(1,1-dimethylethyl)-5-isoxazolyl]-2,6-diethylbenzamide

M.P. 173°-175° C. Yield 7%.

Analysis calculated for C₁₈ H₂₄ N₂ O₂ ; Theory: C, 71.97; H, 8.05; N,9.33. Found: C, 72.20; H, 8.24; N, 9.21.

EXAMPLE 60N-[3-(1,1-dimethylethyl)-5-isoxazolyl]-2,4,6-trimethoxybenzamide

M.P. 115°-118° C. Yield 26%.

Analysis calculated for C₁₇ H₂₂ N₂ O₅ ; Theory: C, 61.07; H, 6.63; N,8.38; Found: C, 60.88; H, 6.76; N, 8.12.

EXAMPLE 61N-[5-(1-ethyl-1-methylpropyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide(A) Preparation of 2-amino-5-(1-ethyl-1-methylpropyl)-1,3,4-thiadiazole

A solution containing 13.0 g of 2-ethyl-2-methylbutyric acid and 9.1 gof thiosemicarbazide in 125 ml of dioxane was stirred and heated to 90°C. To the stirred reaction mixture was added dropwise over thirtyminutes 15.3 g of phosphorous oxychloride. Following complete addition,the reaction mixture was heated at 90° C. for six hours. The mixture wasthen cooled to about 30° C. and added to 100 g of ice. The aqueousmixture was made alkaline by the addition of ammonium hydroxide, and thealkaline solution was extracted several times with ethyl acetate. Theextracts were combined, washed with water, dried, and the solvent wasremoved by evaporation under reduced pressure to afford 17.0 g of2-amino-5-(1-ethyl-1-methylpropyl)-1,3,4-thiadiazole.

M.P. 138°-140° C.

(B)

To a stirred solution of 9.2 g of the thiadiazole from above in 100 mlof tetrahydrofuran containing 4.0 g of pyridine were added in oneportion 11.0 g of 2,6-dimethoxybenzoyl chloride. The reaction mixturewas heated at reflux for three hours, and then cooled to about 30° C.and filtered. The solvent was removed from the filtrate by evaporationunder reduced pressure to provide a solid which, when crystallized from2B ethanol afforded 6.3 g ofN-[5-(1-ethyl-1-methylpropyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide.

M.P. 208°-210° C. Yield 36%.

Analysis calculated for C₁₇ H₂₃ N₃ O₃ S: Theory: C, 58.43; H, 6.63; N,12.02. Found: C, 58.34; H, 6.58; N, 11.79.

EXAMPLE 62N-[5-(1-ethyl-1-methylpropyl)-1,3,4-thiadiazol-2-yl]-benzamide

To a stirred suspension of 3.3 g of2-amino-5-(1-ethyl-1-methylpropyl)-1,3,4-thiadiazole in 30 ml oftetrahydrofuran were added in one portion 2.8 g of benzoyl chloride. Thereaction mixture was stirred at room temperature while a solution of 1.6g of pyridine in 20 ml of tetrahydrofuran was added dropwise over thirtyminutes. Following complete addition, the reaction mixture was heated atreflux for three hours. The mixture was then filtered to remove thepyridine hydrochloride, and the filtrate was washed several times with1N hydrochloric acid solution. The organic layer was separated and thesolvent was removed by evaporation under reduced pressure to provide ayellow gum. The gum was crystallized from the ethanol and water toafford 1.85 g ofN-[5-(1-ethyl-1-methylpropyl)-1,3,4-thiadiazol-2-yl]benzamide.

M.P. 98°-100° C. Yield 35%.

Analysis calculated for C₁₅ H₁₉ N₃ OS; Theory: C, 62.25; H, 6.62; N,14.52; S, 11.08. Found: C, 62.01; H, 6.39; N, 14.27; S, 11.22.

EXAMPLE 63N-[5-(1-ethyl-1-methylpropyl)-1,3,4-thiadiazol-2-yl]-2,6-diethylbenzamide(A) Preparation of 2,6-diethylbenzoyl chloride

2,6-Diethylcyanobenzene was prepared by converting 2,6-diethylaniline toa diazonium salt and then reacting the diazonium salt with coppercyanide. Hydrolysis of 2,6-diethylcyanobenzene was effected by reactionwith sodium hydroxide in ethylene glycol to provide2,6-diethylaminocarbonyl benzene. The latter compound was reacted withphosphoric acid to provide 2,6-diethylbenzoic acid. Reaction of thebenzoic acid with thionyl chloride afforded 2,6-diethylbenzoylchlorideas an oil.

(B)

A solution of 1.85 g of2-amino-5-(1-ethyl-1-methylpropyl)-1,3,4-thiadiazole and 2.21 g of2,6-diethylbenzoyl chloride in 50 ml of toluene was heated at reflux forsixteen hours and then cooled and the solvent was removed by evaporationunder reduced pressure to provide a solid residue. The solid wascrystallized from 2B ethanol to give 1.25 g ofN-[5-(1-ethyl-1-methylpropyl)-1,3,4-thiadiazol-2-yl]-2,6-diethylbenzamide.

M.P. 186°-188° C. Yield 36%.

Analysis calculated for C₁₉ H₂₇ N₃ OS: Theory: C, 66.05; H, 7.88; N,12.16; S, 9.28. Found: C, 66.18; H, 7.82; N, 11.87; S, 9.16.

EXAMPLE 64N-[5-(1,1-dimethyl-2-(methylthio)ethyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide(A) Preparation of2-amino-5-[1,1-dimethyl-2-(methylthio)ethyl]-1,3,4-thiadiazole

Lithium diisopropylamide was prepared by reacting 51.0 g ofdiisopropylamine with 227 ml of n-butyl lithium in 350 ml oftetrahydrofuran at -5° C. To the stirred reaction mixture were addeddropwise over thirty minutes 22.0 g of isobutyric acid. Following theaddition, the reaction mixture was warmed to 25° C. and stirred for onehour. The mixture was then again cooled to -5° C., and 24.1 g ofchloromethyl methylsulfide were added dropwise. The reaction mixture wasallowed to warm to 25° C. and was stirred at that temperature for twelvehours. The excess solvent was next removed by evaporation under reducedpressure, and the residue was added to 50 g of ice containing 50 ml of1N hydrochloric acid solution. The aqueous acid mixture was extractedseveral times with diethyl ether, and the extracts were combined, washedwith water, dried, and the solvent was removed by evaporation to give22.0 g of 2,2-dimethyl-methylthiopropionic acid as an oil.

A 9.0 g portion of the acid thus formed was dissolved in 120 ml ofdioxane containing 5.5 g of thiosemicarbazide, and the reaction mixturewas heated at 90° C. for thirty minutes, and then a 10.1 g portion ofphosphorus oxychloride was added dropwise over ten minutes to thereaction mixture. Following complete addition, the mixture was heated at90° C. for twelve hours. After cooling the reaction mixture to roomtemperature, the solvent was decanted and the solid precipitate wasdissolved in warm water. The aqueous mixture was made alkaline to pH 8by the addition of ammonium hydroxide, and then the alkaline solutionwas extracted with ethyl acetate. The extracts were combined, washedwith water, dried, and the solvent was removed by evaporation underreduced pressure to provide 4.2 g of2-amino-5-[1,1-dimethyl-2-(methylthio)ethyl]-1,3,4-thiadiazole.

M.P. 117°-120° C.

(B) A 3.0 g portion of the thiadiazole thus prepared was reacted with3.4 g of 2,6-dimethoxybenzoyl chloride in 30 ml of tetrahydrofurancontaining 1.3 g of pyridine. The reaction was carried out at 106° C.for sixteen hours. After cooling the reaction mixture to roomtemperature, the solvent was removed by evaporation under reducedpressure to leave the product as an oil. The oil was purified first bychromatography over silica gel using diethyl ether as an eluant, andthen by crystallization from ethyl acetate to provide 1.94 g ofN-[5-(1,1-dimethyl-2-(methylthio)ethyl]-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide.

M.P. 165°-167° C. Yield 35%.

Analysis calculated for C₁₆ H₂₁ N₃ O₃ S₂ : Theory: C, 52.29; H, 5.76; N,11.43; S, 17.45. Found: C, 52.38; H, 5.47; N, 11.20; S, 17.40.

By following the general procedures of Examples 61-64, an appropriatelysubstituted 2-amino-1,3,4-thiadiazole was reacted with a benzoyl halidederivative to provide the following exemplaryN-(1,3,4-thiadiazol-2-yl)benzamides.

EXAMPLE 65N-[5-(1-cyclohexyl-1-methylethyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide.

M.P. 241°-243° C. Yield 38%.

Analysis calculated for C₂₀ H₂₇ N₃ O₃ S: Theory: C, 61.67; H, 6.99; N,10.79. Found: C, 61.68; H, 6.76; N, 10.77.

EXAMPLE 66N-[5-(1,1-diethylpropyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide.

M.P. 216°-218° C. Yield 31%.

Analysis calculated for C₁₈ H₂₅ N₃ O₃ S: Theory: C, 59.48; H, 6.93; N,11.56. Found: C, 59.65; H, 6.73; N, 11.37.

EXAMPLE 67N-[5-(2,2-dimethylpropyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide

M.P. 188°-190° C. Yield 43%.

Analysis calculated for C₁₆ H₂₁ N₃ O₃ S: Theory: C, 57.29; H, 6.31; N,12.53. Found: C, 57.27; H, 6.10; N, 12.31.

EXAMPLE 68N-[5-(2-methoxy-1,1-dimethylethyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide

M.P. 172°-174° C. Yield 56%.

Analysis calculated for C₁₆ H₂₁ N₃ O₄ S: Theory: C, 54.68; H, 6.02; N,11.96. Found: C, 54.56; H, 5.95; N, 11.72.

EXAMPLE 69N-[5-(1,1-dimethyl-2-phenylethyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide

M.P. 167°-169° C. Yield 29%.

Analysis calculated for C₂₁ H₂₃ N₃ O₃ S: Theory: C, 63.45; H, 5.83; N,10.57; S, 8.07. Found: C, 63.71; H, 5.82; N, 10.71; S, 8.05.

EXAMPLE 70N-[5-(2-cyclohexyl-1,1-dimethylethyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide

M.P. 191°-193° C. Yield 77%.

Analysis calculated for C₂₁ H₂₉ N₃ O₃ S: Theory: C, 62.50; H, 7.24; N,10.41; S, 7.95. Found: C, 62.63; H, 7.22; N, 10.43; S, 7.99.

EXAMPLE 71N-[5-(1,1-dimethylhexyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide

M.P. 120°-122° C. Yield 66%.

Analysis calculated for C₁₉ H₂₇ N₃ O₃ S: Theory: C, 60.45; H, 7.21; N,11.13; S, 8.49. Found: C, 60.64; H, 7.00; N, 11.27; S, 8.75.

EXAMPLE 72N-[5-(1-ethyl-1-methylpropyl)-1,3,4-thiadiazol-2-yl]-2-methoxy-3,6-dichlorobenzamide

M.P. 194°-196° C. Yield 6%.

Analysis calculated for C₁₆ H₁₉ Cl₂ N₃ O₂ S: Theory: C, 49.49; H, 4.93;N, 10.82. Found: C, 49.69; H, 5.10; N, 11.04.

EXAMPLE 73N-[5-(1-ethylpentyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide

M.P. 120°-122° C. Yield 69%.

Analysis calculated for C₁₈ H₂₅ N₃ O₃ S: Theory: C, 59.48; H, 6.93; N,11.56. Found: C, 59.74; H, 6.90; N, 11.45.

EXAMPLE 74N-[5-(1-methylcyclohexyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide

M.P. 211°-213° C. Yield 47%.

Analysis calculated for C₁₁ H₂₃ N₃ O₃ S: Theory: C, 59.81; H, 6.41; N,11.63. Found: C, 60.03; H, 6.13; N, 11.83.

EXAMPLE 75N-[5-(1-methylpropyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide

M.P. 137°-140° C. Yield 27%.

Analysis calculated for C₁₅ H₁₉ N₃ O₃ S: Theory: C, 56.06; H, 5.96; N,13.07. Found: C, 56.27; H, 6.03; N, 12.85.

EXAMPLE 76N-[5-(1-ethyl-1-methylbutyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide

M.P. 145°-146° C. Yield 15%.

Analysis calculated for C₁₈ H₂₅ N₃ O₃ S: Theory: C, 59.48; H, 6.93; N,11.56. Found: C, 59.33; H, 7.03; N, 11.49.

EXAMPLE 77N-[5-(cyclohexylmethyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide

M.P. 152°-154° C. Yield 54%.

Analysis calculated for C₁₈ H₂₃ N₃ O₃ S: Theory: C, 59.81; H, 6.41; N,11.63, S, 8.87. Found: C, 59.87; H, 6.40; N, 11.34; S, 8.62.

EXAMPLE 78N-[5-(2,2-dimethylbutyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide

M.P. 168°-169° C. Yield 42%.

Analysis calculated for C₁₇ H₂₃ N₃ O₃ S: Theory: C, 58.43; H, 6.63; N,12.02. Found: C, 58.70; H, 6.79; N, 11.77.

EXAMPLE 79N-[5-(1-methylcyclopropyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide

M.P. 197°-198° C. Yield 41%.

Analysis calculated for C₁₅ H₁₇ N₃ O₃ S: Theory: C, 56.41; H, 5.37; N,13.16. Found: C, 56.19; H, 5.25; N, 12.99.

EXAMPLE 80N-[5-(1-methylcyclopentyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide

M.P. 218°-220° C. Yield 22%.

Analysis calculated for C₁₇ H₂₁ N₃ O₃ S: Theory: C, 58.77; H, 6.09; N,12.09. Found: C, 58.98; H, 6.34; N, 12.09.

EXAMPLE 81N-[5-(2,2-dichloro-1-methylcyclopropyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide

M.P. 235°-236° C. Yield 63%.

Analysis calculated for C₁₅ H₁₅ Cl₂ N₃ O₃ S: Theory: C, 46.40; H, 3.89;N, 10.82. Found: C, 46.66; H, 3.64; N, 10.60.

EXAMPLE 82N-[5-(1,2-dimethylpropyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide

M.P. 169°-171° C. Yield 50%.

Analysis calculated for C₁₆ H₂₁ N₃ O₃ S: Theory: C, 57.29; H, 6.31; N,12.53. Found: C, 57.29; H, 6.02; N, 12.37.

EXAMPLE 83N-[5-(1,1-dimethyl-3-butenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide

M.P. 170°-172° C. Yield 38%.

Analysis calculated for C₁₇ H₂₁ N₃ O₃ S: Theory: C, 58.77; H, 6.09; N,12.09, S, 9.23. Found: C, 58.75; H, 5.89; N, 11.91; S, 8.98.

EXAMPLE 84N-[5-(1-ethyl-1-methylpropyl)-1,3,4-thiadiazol-2-yl]-2-chlorobenzamide

M.P. 233°-234° C. Yield 49%.

Analysis calculated for C₁₅ H₁₈ ClN₃ OS: Theory: C, 55.63; H, 5.60; N,12.98. Found: C, 55.40; H, 5.36; N, 12.81.

EXAMPLE 85N-[5-(1-ethyl-1-methylpropyl)-1,3,4-thiadiazol-2-yl]-2-methoxybenzamide

M.P. 114°-115° C. Yield 25%.

Analysis calculated for C₁₆ H₂₁ N₃ O₂ S: Theory: C, 60.16; H, 6.63; N,13.16. Found: C, 59.96; H, 6.42; N, 13.05.

EXAMPLE 86N-[5-(1-ethyl-1-methylpropyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethylbenzamide

M.P. 191°-192° C. Yield 32%.

Analysis calculated for C₁₇ H₂₃ N₃ OS: Theory: C, 64.32; H, 7.30; N,13.24. Found: C, 64.47; H, 7.41; N, 13.46.

EXAMPLE 87N-[5-(1-ethyl-1-methylpropyl)-1,3,4-thiadiazol-2-yl]-2-(methylthio)benzamide

M.P. 145°-147° C. Yield 62.1%.

Analysis calculated for C₁₆ H₂₁ N₃ OS₂ : Theory: C, 57.28; H, 6.31; N,12.53; S, 19.11. Found: C, 56.99; H, 6.06; N, 12.50; S, 19.35.

EXAMPLE 88N-[5-(1-ethylcyclohexyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide

M.P. 222°-224° C. Yield 25%.

Analysis calculated for C₁₉ H₂₅ N₃ O₃ S: Theory: C, 60.78; H, 6.71; N,11.19. Found: C, 60.63; H, 6.85; N, 10.92.

EXAMPLE 89N-[5-(1,1-diethylbutyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide

M.P. 210°-212° C. Yield 61%.

Analysis calculated for C₁₉ H₂₇ N₃ O₃ S: Theory: C, 60.45; H, 7.21; N,11.13. Found: C, 60.47; H, 6.94; N, 10.97.

EXAMPLE 90N-[5-(1,1,2-trimethylpropyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide

M.P. 197°-199° C. Yield 22%.

Analysis calculated for C₁₇ H₂₃ N₃ O₃ S: Theory: C, 58.43; H, 6.63; N,12.02; S, 9.18. Found: C, 58.66; H, 6.43; N, 12.02; S, 9.03.

EXAMPLE 91N-[5-(1-ethylcyclopentyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide

M.P. 226°-228° C. Yield 62%.

Analysis calculated for C₁₈ H₂₃ N₃ O₃ S: Theory: C, 59.81; H, 6.41; N,11.63; S, 8.87. Found: C, 59.91; H, 6.16; N, 11.71; S, 9.08.

EXAMPLE 92N-[5-(1-ethyl-1-methylpropyl)-1,3,4-thiadiazol-2-yl]-2,6-dichlorobenzamide

M.P. 276°-277° C. Yield 39%.

Analysis calculated for C₁₅ H₁₇ Cl₂ N₃ OS: Theory: C, 50.28; H, 4.78; N,11.73; S, 8.95; Cl, 19.79. Found: C, 50.52; H, 4.54; N, 11.56; S, 8.69;Cl, 20.03.

EXAMPLE 93 N-(5-methyl-1,3,4-thiadiazol-2-yl)-2,6-dimethoxybenzamide

M.P. 187°-188° C. Yield 85%.

Analysis calculated for C₁₂ H₁₃ N₃ O₃ S: Theory: C, 51.60; H, 4.69; N,15.04. Found: C, 51.72; H, 4.50; N, 15.05.

EXAMPLE 94N-[5-(methoxymethyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide

M.P. 164°-166° C. Yield 51%.

Analysis calculated for C₁₃ H₁₅ N₃ O₄ S: Theory: C, 50.48; H, 4.89; N,13.58; S, 10.37. Found: C, 50.63; H, 4.74; N, 13.37; S, 10.39.

EXAMPLE 95N-[5-(1-methyl-1-propylbutyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide

M.P. 161°-163° C. Yield 40%.

Analysis calculated for C₁₉ H₂₇ N₃ O₃ S: Theory: C, 60.45; H, 7.21; N,11.13; S, 8.49. Found: C, 60.66; H, 7.03; N, 10.85; S, 8.27.

EXAMPLE 96N-[5-(1,1,2,2-tetramethylpropyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide

M.P. 245°-247° C. Yield 51%.

Analysis calculated for C₁₈ H₂₅ N₃ O₃ S: Theory: C, 59.48; H, 6.93; N,11.56; S, 8.82. Found: C, 59.58; H, 6.70; N, 11.44; S, 8.93.

EXAMPLE 97N-[5-(1-ethyl-1-methylpropyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxy-4-(trifluoromethyl)benzamide

M.P. 252°-254° C. Yield 20%.

Analysis calculated for C₁₈ H₂₂ F₃ N₃ O₃ S: Theory: C, 51.79; H, 5.31;N, 10.07; S, 7.68; F, 13.65. Found: C, 51.52; H, 5.07; N, 9.97; S, 7.84;F, 13.70.

EXAMPLE 98N-[5-(2-chloro-1,1-dimethylethyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide

M.P. 202°-204° C. Yield 69%.

Analysis calculated for C₁₅ H₁₈ ClN₃ O₃ S: Theory: C, 50.63; H, 5.06; N,11.81; S, 9.00. Found: C, 50.86; H, 5.14; N, 11.90; S, 8.59.

EXAMPLE 99N-[5-(1,1-dimethylpentyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide

M.P. 160°-162° C. Yield 30%.

Analysis calculated for C₁₈ H₂₅ N₃ O₃ S: Theory: C, 59.48; H, 6.93; N,11.56; S, 8.82. Found: C, 59.69; H, 6.77; N, 11.34; S, 8.81.

EXAMPLE 100N-(5-cyclohexyl-1,3,4-thiadiazol-2-yl)-2,6-dimethoxybenzamide

M.P. 206°-208° C. Yield 55%.

Analysis calculated for C₁₇ H₂₁ N₃ O₃ S: Theory: C, 58.77; H, 6.09; N,12.09; S, 9.23. Found: C, 58.48; H, 6.30; N, 11.85; S, 9.42.

EXAMPLE 101N-[5-(1,1-dimethylbutyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide

M.P. 167°-169° C. Yield 45%.

Analysis calculated for C₁₇ H₂₃ N₃ O₃ S: Theory: C, 58.43; H, 6.63; N,12.02; S, 9.18. Found: C, 58.65; H, 6.79; N, 12.25; S, 8.87.

EXAMPLE 102N-(5-cyclobutyl-1,3,4-thiadiazol-2-yl)-2,6-dimethoxybenzamide

M.P. 195°-197° C. Yield 65%.

Analysis calculated for C₁₅ H₁₇ N₃ O₃ S: Theory: C, 56.41; H, 5.37; N,13.16; S, 10.04. Found: C, 56.13; H, 5.18; N, 12.89; S, 9.96.

EXAMPLE 103N-[5-(1-ethyl-1-methylpropyl)-1,3,4-thiadiazol-2-yl]-4-methoxybenzamide

M.P. 138°-140° C. Yield 63%.

Analysis calculated for C₁₆ H₂₁ N₃ O₂ S: Theory: C, 60.16; H, 6.63; N,13.16; S, 10.04. Found: C, 59.90; H, 6.47; N, 13.10; S, 9.82.

EXAMPLE 104N-[5-(1-ethyl-1-methylpropyl)-1,3,4-thiadiazol-2-yl]-2,4,6-trimethyoxybenzamide

M.P. 183.5° C. Yield 65%.

Analysis calculated for C₁₈ H₂₅ N₃ O₄ S: Theory: C, 56.97; H, 6.64; N,11.07; S, 8.45. Found: C, 57.15; H, 6.63; N, 10.86; S, 8.38.

EXAMPLE 105N-[5-(1-propylcyclohexyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide

M.P. 190°-192° C. Yield 56%.

Analysis calculated for C₂₀ H₂₇ N₃ O₃ S: Theory: C, 61.67; H, 6.99; N,10.79; S, 8.23; Found: C, 61.46; H, 6.76; N, 10.53; S, 8.44.

EXAMPLE 106N-[5-(1,1,2-trimethyl-2-butenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide

M.P. 215°-218° C. Yield 60%.

Analysis calculated for C₁₈ H₂₃ N₃ O₃ S: Theory: C, 59.81; L H, 6.41; N,11.63; S, 8.87; Found: C, 59.54; H, 6.14; N, 11.55; S, 8.80.

EXAMPLE 107N-[5-(1,1,2-trimethylbutyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide

M.P. 181°-183° C. Yield 69%.

Analysis calculated for C₁₈ H₂₅ N₃ O₃ S: Theory: C, 59.48; H, 6.93; N,11.56; S, 8.82; Found: C, 59.46; H, 6.61; N, 11.36; S, 8.32.

EXAMPLE 108N-[5-(1,1,3-trimethylbutyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide

M.P. 195°-197° C. Yield 66%.

Analysis calculated for C₁₈ H₂₅ N₃ O₃ S: Theory: C, 59.48; H, 6.93; N,11.56; Found: C, 59.40; H, 6.77; N, 11.58.

EXAMPLE 109N-[5-(1,1-dimethylpropyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide

M.P. 227°-229° C. Yield 67%.

Analysis calculated for C₁₆ H₂₁ N₃ O₃ S: Theory: C, 57.29; H, 6.31; N,12.53; S, 9.56; Found: C, 57.09; H, 6.03; N, 12.27; S, 9.76.

EXAMPLE 110N-[5-phenylmethyl-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide

M.P. 190°-192° C. Yield 80%.

Analysis calculated for C₁₈ H₁₇ N₃ O₃ S: Theory: C, 60.83; H, 4.82; N,11.82; S, 9.02; Found: C, 60.78; H, 4.86; N, 12.05; S, 8.88.

EXAMPLE 111N-[5-(1,1-dimethylethyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide

M.P. 230°-232° C. Yield 77%.

Analysis calculated for C₁₅ H₁₉ N₃ O₃ S: Theory: C, 56.05; H, 5.96; N,12.07; Found: C, 55.81; H, 5.98; N, 12.10.

EXAMPLE 112N-[5-(1-ethyl-1,2,2-trimethylpropyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide

M.P. 254°-256° C. Yield 56%.

Analysis calculated for C₁₉ H₂₇ N₃ O₃ S: Theory: C, 60.45; H, 7.21; N,11.13; S, 8.49; Found: C, 60.33; H, 7.02; N, 10.95; S, 8.80.

EXAMPLE 113N-(5-cyclopentyl-1,3,4-thiadiazol-2-yl)-2,6-dimethoxybenzamide

M.P. 180°-181° C. Yield 72%.

Analysis calculated for C₁₆ H₁₉ N₃ O₃ S: Theory: C, 57.64; H, 5.74; N,12.60; Found: C, 57.70; H, 5.87; N, 12.37.

EXAMPLE 114N-[3-(1,1-dimethylethyl)-1H-pyrazol-5-yl]-2,6-dimethoxybenzamide (A)Preparation of 3-(1,1-dimethylethyl)-5-amino-1H-pyrazole

A suspension of 9.6 g of sodium hydride in 300 ml of tetrahydrofuran wasstirred at 60° C. while a mixture of 23.2 g of methyl trimethylacetateand 8.2 g of acetonitrile was added in one portion. The reaction mixturewas heated at reflux for five hours, and then cooled to room temperatureand concentrated by evaporation of the solvent under reduced pressure.The product thus formed was dissolved in water and washed withdichloromethane. The aqueous layer was made acidic with 1N hydrochloricacid, and the acidic solution was extracted with fresh dichloromethane.The organic extracts were combined, washed with water, dried, and thesolvent was removed by evaporation to give 14.0 g of cyanomethyltert.-butyl ketone.

The ketone thus formed was dissolved in 150 ml of ethanol containing 32g of hydrazine. The reaction mixture was heated at reflux for twelvehours, and then cooled to room temperature. Removal of the solvent byevaporation under reduced pressure provided a solid residue, which whentriturated with 250 ml of petroleum ether, filtered and air dried, wasidentified as 12.5 g of 3-tert.-butyl-5-amino-1H-pyrazole.

M.P. 72°-74° C.

(B) Acylation of the amino pyrazole with 2,6-dimethoxybenzoyl chloride.

To a stirred solution of 1.39 g of 3-tert.-butyl-5-amino-1H-pyrazole in50 ml of benzene were added in one portion 2.01 g of2,6-dimethoxybenzoyl chloride. The reaction mixture was heated at refluxfor sixteen hours. The reaction mixture was then cooled, filtered, andthe solvent was removed from the filtrate by evaporation. The residuewas crystallized from ethyl acetate to provide 550 mg ofN-[3-(1,1-dimethylethyl)-1H-pyrazol-5-yl]-2,6-dimethoxybenzamide.

M.P. 176°-178° C. Yield 18%.

Mass Spec. M⁺ Theory, 303; Found 304.

NMR (DMSOd₆): δ 1.35 (s, 9H, t-Bu); δ 3.76 (s, 6H, CH₃ O--) δ 5.7-7.4(m, 5H, aromatic); δ 10.9 (s, 1H, amide NH).

Analysis calculated for C₁₆ H₂₁ N₃ O₄ : Theory: C, 63.35; H, 6.98; N,13.85; Found: C, 57.39; H, 6.34; N, 14.41.

The following N-pyrazolyl benzamides were prepared by the generalprocedure of Example 114.

EXAMPLE 115N-[3-(1-ethyl-1-methylpropyl)-1H-pyrazol-5-yl]-2,6-dimethoxybenzamide

M.P. 222°-223° C. Yield 38%.

Analysis calculated for C₁₈ H₂₅ N₃ O₃ Theory: C, 65.23; H, 7.60; N,12.68; Found: C, 65.08; H, 7.61; N, 12.50.

EXAMPLE 116N-[3-(1,1-dimethylbutyl)-1H-pyrazol-5-yl]-2,6-dimethoxybenzamide

M.P. 211°-213° C. Yield 27%.

Mass Spec. M⁺ Theory, 330; Found, 331.

NMR (CDCl₃): δ 0.7-1.6 (m, 13H, 1,1-dimethylbutyl); δ 3.81 (s, 6H, CH₃O); δ 6.51-6.77 (m, 3H, benzoyl aromatic); δ 7.2-7.5 (m, 2H, pyrazolearomatic); δ 7.8-8.1 (broad s, 1H, amide NH).

Analysis calculated for C₁₈ H₂₄ N₃ O₃ : Theory: C, 65.23; H, 7.60; N,12.68; Found: C, 65.34; H, 6.79; N, 8.44.

EXAMPLE 117N-[3-(1,1-dimethylpropyl)-1H-pyrazol-5-yl]-2,6-dimethoxybenzamide

M.P. 235°-237° C. Yield 37%.

Analysis calculated for C₁₇ H₂₂ N₃ O₃ : Theory: C, 64.33; H, 7.30; N,13.24; Found: C, 64.20; H, 7.03; N, 12.99.

EXAMPLE 118N-[5-(1-ethyl-1-methylpropyl)-4H-1,2,4-triazol-3-yl]-2,6-dimethoxybenzamide(A) Preparation of 5-(1-ethyl-1-methylpropyl)-3-amino-4H-1,2,4-triazole

To a stirred solution of 13.1 g of potassium hydroxide in 40 ml of waterwere added dropwise a solution of 8.4 g of dicyandiamide in 50 ml ofacetone. The reaction mixture was next cooled to 5° C., and then 14.0 gof 2-ethyl-2-methyl butyryl chloride were added dropwise over tenminutes. Following the addition, the reaction mixture was stirred atabout 5° C. for fifteen minutes, and then diluted to 600 ml by theaddition of water. The aqueous mixture was made acidic to pH 5.5 withglacial acetic acid, whereupon a white precipitate formed. Theprecipitate was collected by filtration, washed with water and air driedto give 5.45 g of N-(2-ethyl-2-methylbutyryl)dicyandiamide.

The product thus formed was suspended in 35 ml of water and stirredwhile a solution of 1.1 g of hydrazine in 25 ml of 2-ethoxyethanol wasadded in one portion. The reaction mixture was boiled for forty-fiveminutes, and then was cooled to room temperature and stirred for twelvehours. The precipitate which had formed was collected by filtration andwas dried at 90° C. for two hours to provide 2.65 g of1-[5-(1-ethyl-1-methylpropyl)-4H-1,2,4-triazol-3-yl]urea.

The pyrazolyl urea thus formed was added to 30 ml of water containing3.0 g of sodium hydroxide. The reaction mixture was heated at reflux fortwelve hours, and then made strongly acidic (pH 2.0) with nitric acid.The precipitate which formed was collected by filtration while themixture was hot. After air drying the precipitate, it was identified as2.65 g of 5-(1-ethyl-1-methylpropyl)-3-amino-4H-1,2,4-triazole, as thenitric acid salt.

M.P. 131° C.

The salt thus formed was dissolved in water and diluted with ammonia topH 8. The solvent was then removed by evaporation and the residue wastriturated with 25 ml of acetonitrile to give 1.1 g of5-(1-ethyl-1-methylpropyl-3-amino-4H-1,2,4-triazole.

(B)

A solution of 1.1 g of the triazole and 1.43 g of 2,6-dimethoxybenzoylchloride in 75 ml of toluene was heated at reflux for sixteen hours. Thereaction mixture was cooled to room temperature and the solvent wasremoved by evaporation under reduced pressure to give a gum. The gum waschromatographed over a silica gel column, eluting with 50% ethyl acetatein hexane. The fractions shown by thin layer chromatographic analysis tocontain the product were combined and the solvent was evaporated toprovide 175 mg ofN-[5-(1-ethyl-1-methylpropyl)-4H-1,2,4-triazol-3-yl]-2,6-dimethoxybenzamide.

M.P. 279°-280° C. Yield 8%.

Analysis calculated for C₁₇ H₂₄ N₄ O₃ : Theory: C, 61.45; H, 7.23; N,16.87; Found: C, 60.94; H, 7.14; N, 15.99.

Mass Spec: M⁺ Theory, 332, Found, 333.

EXAMPLE 119

2,6-Dimethoxybenzoyl chloride was reacted with 3-amino-1H-1,2,4-triazoleaccording to the procedure of Example 118 to provideN-(1H-1,2,4-triazol-3-yl)-2,6-dimethoxybenzamide.

M.P. 191°-193° C.

EXAMPLE 120N-[3-(1,1-dimethylethyl)-5-isothiazolyl]-2,6-dimethoxybenzamide (A)Preparation of 3-(1,1-dimethylethyl)-5-aminoisothiazole

A mixture of 50.0 g of cyanomethyl tert.-butyl ketone in 250 ml ofethanol containing 200 ml of ammonia was heated at 150° C. for sixteenhours. The reaction mixture was cooled to room temperature and thesolvent was removed by evaporation under reduced pressure. The residuewas dissolved in 330 ml of dichloromethane and diluted with 0.7 g ofpotassium hydroxide and 52 ml of hydrogen sulfide. The reaction mixturewas heated at 80° C. for twenty-four hours, and then cooled andconcentrated to dryness by evaporation of the solvent. The product wasidentified as 71 g of 2,2-dimethyl-3-amino-3-butenyl thiocarboxamide.

An 800 mg portion of the product thus obtained was dissolved in 25 ml ofethanol containing 5 ml of 30% hydrogen peroxide. The reaction mixturewas stirred for twenty minutes, and then concentrated to dryness byevaporation to provide (3-(1,1-dimethyl-ethyl)-5-aminoisothiazole.

(B)

A solution of the 5-amino-isothiazole and 1.1 g of 2,6-dimethoxybenzoylchloride in 50 ml of toluene was heated at reflux for two hours, duringwhich time a precipitate formed. The precipitate was collected byfiltration and dried to give 340 mg ofN-[3-(1,1-dimethylethyl)-5-isothiazolyl]-2,6-dimethoxybenzamide.

M.P. 266°-267° C. Yield 30%.

Analysis claculated for C₁₆ H₂₀ N₂ O₃ S: Theory: C, 59.98; H, 6.29; N,8.74; Found: C, 59.71; H, 6.15; N, 8.74.

EXAMPLE 121

N-[3-(1-ethyl-1-methylpropyl)-5-isothiazolyl]-2,6-dimethoxybenzamide wasprepared according to Example 120.

M.P. 243°-244° C. Yield 70%.

Analysis calculated for C₁₈ H₂₄ N₂ O₃ S: Theory: C, 62.04; H, 6.94; N,8.04; Found: C, 62.21; H, 6.73; N, 8.24.

EXAMPLE 122N-[6-(1,1-dimethylethyl)pyridazin-3-yl]-2,6-dimethoxybenzamide (A)Preparation of 3-amino-6-(1,1-dimethylethyl)pyridazine

A mixture of 5.8 of 3-chloro-6-(1,1-dimethylethyl)pyridazine in 100 ml.of liquid ammonia was heated in a bomb at 200° C. for twenty-four hours.The reaction mixture was cooled to room temperature and filtered, andthe solvent was removed from the filtrate by evaporation under reducedpressure to provide a black oil. The oil was chromatographed over silicagel, eluting with ethyl acetate and benzene. The appropriate fractionswere combined and the solvent was removed therefrom by evaporation togive 2.08 g. of 3-amino-6-(1,1-dimethylethyl)pyridazine. M.P. 125°-132°C.

Analysis calculated for C₈ H₁₃ N₃ : Theory: C, 63.54; H, 8.67; N, 27.79;Found: C, 63.74; H, 8.49; N, 27.53.

(B) A solution of 600 mg. of 2,6-dimethoxybenzoyl chloride in 100 ml. oftoluene containing 500 mg. of 3-amino-6-(1,1-dimethylethyl)pyridazinewas heated at reflux under a nitrogen atmosphere for twenty-one hours.The reaction mixture was cooled to room temperature and the precipitatewhich formed was collected by filtration. The solid product waschromatographed over silica gel, eluting with ethyl acetate. Thin layerchromatographic analysis of the major product suggested that a minoramount of bis acylated product had been formed. The mixture wasdissolved in 10 ml. of ethanol and 10 ml. of 2N sodium hydroxide, andthe alkaline solution was heated at reflux for two hours. The reactionmixture was cooled and acidified by the addition of 1N hydrochloricacid. The precipitate which formed was collected by filtration andrecrystallized from hexane to provide 49 mg. ofN-[6-(1,1-dimethylethyl)pyridazin-3-yl]-2,6-dimethoxybenzamide.

M.P. 163°-165° C. Yield 5%.

Analysis calculated for C₁₇ H₂₁ N₃ O₃ : Theory: C, 64.74; H, 6.71; N,13.32; Found: C, 64.95; H, 6.41; N, 13.28.

Mass Spec. M⁺ Theory 315; Found 315.

Several additional compounds embraced by this invention have beenprepared by reaction of an appropriately substituted benzoyl halide witha aryl amine. Typical examples follow.

EXAMPLE 123N-[5-(1-ethyl-1-methylpropyl)-1,3,4-thiadiazol-2-yl]-2,6-di(methylthio)benzamide

M.P. 194°-195° C. Yield 42%.

Analysis calculated for C₁₇ H₂₃ N₃ OS₃ : Theory: C, 53.51; H, 6.08; N,11.01; S, 25.21; Found: C, 53.65; H, 6.12; N, 10.80; S, 25.40.

EXAMPLE 124N-[5-(1-ethyl-1-methylpropyl)-1,3,4-thiadiazol-2-yl]-2-methoxy-6-methylthiobenzamide

M.P. 184°-185° C. Yield 44.7%.

Analysis calculated for C₁₇ H₂₃ N₃ O₂ S₂ : Theory: C, 55.86; H, 6.34; N,11.50; S, 17.54; Found: C, 55.93; H, 6.17; N, 11.23; S, 17.37.

EXAMPLE 125N-[5-(1-n-propylcyclopentyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide

M.P. 181°-183° C. Yield 56.5%.

Analysis calculated for C₁₉ H₂₅ N₃ O₃ S: Theory: C, 60.78; H, 6.71; N,11.09; S, 8.54; Found: C, 61.08; H, 6.76; N, 11.40; S, 8.29.

EXAMPLE 126N-[5-(1-(1-methylethenyl)cyclohexyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide

M.P. 226°-228° C. Yield 53%.

Analysis calculated for C₂₀ H₂₅ N₃ O₃ S: Theory: C, 61.99; H, 6.50; N,10.84; S, 8.27; Found: C, 62.20; H, 6.52; N, 10.55; S, 8.04.

EXAMPLE 127N-[5-(1-isopropylcyclohexyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide

M.P. 224°-226° C. Yield 53.6%.

Analysis calculated for C₂₀ H₂₇ N₃ O₃ S: Theory: C, 61.67; H, 6.99; N,10.79; S, 8.23; Found: C, 61.47; H, 6.75; N, 10.53; S, 8.21.

EXAMPLE 128N-[5-(1-ethyl-1,2-dimethyl-2-propenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide

M.P. 207°-209° C. Yield 10%.

Analysis calculated for C₁₈ H₂₃ N₃ O₃ S: Theory: C, 59.81; H, 6.41; N,11.63; S, 8.87; Found: C, 59.65; H, 6.40; N, 11.56; S, 9.02.

EXAMPLE 129N-[5-(1-ethyl-1-methylpropyl)-1,3,4-thiadiazol-2-yl]-2-methoxy-4-trifluoromethyl-6-methylthiobenzamide

M.P. 224°-225° C. Yield 26.2%.

Analysis calculated for C₁₈ H₂₂ F₃ N₃ O₂ S₂ : Theory: C, 49.87; H, 5.12;N, 9.69; F, 13.15; S, 14.79; Found: C, 49.65; H, 4.92; N, 9.90; F,13.40; S, 14.81.

EXAMPLE 130N-[5-(1-methylethyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide.

M.P. 164°-166° C. Yield 29%.

Analysis calculated for C₁₄ H₁₇ N₃ O₃ S: Theory: C, 54.72; H, 5.54; N,13.68; S, 10.42; Found: C, 54.65; H, 5.52; N, 13.62; S, 10.90.

EXAMPLE 131N-(5-Cyclopropyl-1,3,4-thiadiazol-2-yl)-2,6-dimethoxybenzamide

M.P. 194°-196° C. Yield 52%.

Analysis calculated for C₁₄ H₁₅ N₃ O₃ S: Theory: C, 55.07; H, 4.95; N,13.76; S, 10.50; Found: C, 55.37; H, 5.18; N, 13.66; S, 10.29.

EXAMPLE 132 N-(3-ethyl-5-isoxazolyl)-4-2,6-dimethoxybenzamide

M.P. 132°-134° C. Yield 56.6%.

Analysis calculated for C₁₄ H₁₆ N₂ O₄ : Theory: C, 60.86;l H, 5.84; N,10.14; Found: C, 60.77; H, 5.81; N, 10.03.

EXAMPLE 133 N-(3-methyl-5-isoxazolyl)-2,6-dimethoxybenzamide

M.P. 155°-158° C. Yield 70%.

Analysis calculated for C₁₃ H₁₄ N₂ O₄ : Theory: C, 59.54; H, 5.38; N,10.68; O, 24.40. Found: C, 59.85; H, 5.67; N, 10.40; O, 24.63.

EXAMPLE 134 N-(3-n-hexyl-5-isoxazolyl)-2,6-dimethoxybenzamide

M.P. 119°-121° C.

Analysis calculated for C₁₈ H₂₂ N₂ O₄ : Theory: C, 65.04; H, 7.28; N,8.43; Found: C, 64.92; H, 7.43; N, 8.16.

EXAMPLE 135 N-(3-ethyl-5-isoxazolyl)-2,6-dimethoxybenzamide

M.P. 132°-134° C. Yield 56.6%.

Analysis calculated for C₁₄ H₁₆ N₂ O₄ : Theory: C, 60.86; H, 5.84; N,10.14; Found: C, 60.77; H, 5.81; N, 10.03.

EXAMPLE 136N-[5-(1-ethyl-1-methylpropyl)-1,3,4-oxadiazol-2-yl]-2,6-dimethoxybenzamide

M.P. 190°-192° C. Yield 16%

Analysis calculated for C₁₇ H₂₃ N₃ O₃ : Theory: C, 61.36; H, 6.91; N,12.61; Found: C, 61.99; H, 6.84; N, 13.29.

EXAMPLE 137N-[3-(1,1-dimethylethyl)-1,2,4-thiadiazol-5-yl]-2,6-dimethoxybenzamide

M.P. 180°-182° C. Yield 65.7%.

Analysis calculated for C₁₅ H₁₉ N₃ O₃ S: Theory: C, 56.06; H, 5.96; N,13.07; S, 9.98. Found: C, 56.07; H, 5.72; N, 12.89; S, 10.25.

EXAMPLE 138N-[3-(1,1-dimethylethyl-1,2,4-oxadiazol-5-yl]-2,6-dimethoxybenzamide

M.P. 207°-209° C.

Analysis calculated for C₁₅ H₁₉ N₃ O₄ : Theory: C, 59.01; H, 6.27; N,13.76; Found: C, 59.18; H, 6.49; N, 13.85.

EXAMPLE 139N-[3-(1-ethyl-1-methylpropyl)-5-isoxazolyl]-2,3,5-triiodobenzamide

M.P. 167°-168° C.

Analysis calculated for C₁₆ H₁₇ I₃ N₂ O₂ ; Theory: C, 29.56; H, 2.64; N,4.31. Found: C, 29.80; H, 2.79; N, 4.29.

EXAMPLE 140N-[3-(1-ethyl-1-methylpropyl)-5-isoxazolyl]-2,6-di(methylthio)benzamide

M.P. 114°-116° C. Yield 21%.

Analysis calculated for C₁₈ H₂₄ N₂ O₂ S₂ ; Theory: C, 59.31; H, 6.64; N,7.68; S, 17.59. Found: C, 59.20; H, 6.80; N, 7.50; S, 17.51.

EXAMPLE 141N-[3-(1-methoxymethyl)-1-methylpropyl)-5-isoxazolyl]-2,6-dimethoxybenzamide

M.P. 164°-166° C. Yield 34%.

Analysis calculated for C₁₈ H₂₄ N₂ O₅ ; Theory: C, 62.05; H, 6.94; N,8.04. Found: C, 62.34; H, 6.76; N, 8.06.

EXAMPLE 142N-[3-(1-ethyl-1-methylpropyl)-4-methyl-5-isoxazolyl]-2,6-dimethoxybenzamide

M.P. 179°-180° C. Yield 37%.

Analysis calculated for C₁₉ H₂₆ N₂ O₄ ; Theory: C, 65.88; H, 7.57; N,8.09. Found: C, 65.62; H, 7.36; N, 7.86.

EXAMPLE 143N-[5-(1-ethyl-1-methylpropyl)-1,3,4-oxadiazol-2-yl]-2,6-dimethoxybenzamide

M.P. 190°-192° C. Yield 30%.

Analysis calculated for C₁₇ H₂₃ N₃ O₄ ; Theory: C, 61.26; H, 6.91; N,12.61. Found: C, 61.99; H, 6.84; N, 13.29.

EXAMPLE 144N-[5-(1-methylcyclobutyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide

M.P. 218°-220° C. Yield 50.7%.

Analysis calculated for C₁₆ H₁₉ N₃ O₃ S; Theory: C, 57.64; H, 5.74; N,12.60; S, 9.62. Found: C, 57.87; H, 5.87; N, 12.84; S, 9.42.

EXAMPLE 145N-[5-(1,1,2-trimethyl-2-propenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide

M.P. 236°-238° C. Yield 46%.

Analysis calculated for C₁₇ H₂₁ N₃ O₃ S; Theory: C, 58.77; H, 6.09; N,12.09; S, 9.23. Found: C, 58.54; H, 6.24; N, 12.19; S, 9.10.

EXAMPLE 146N-[5(1-ethyl-1-methylpropyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxy-3-bromobenzamide

M.P. 163°-165° C. Yield 35%.

Analysis calculated for C₁₇ H₂₂ BrN₃ O₃ S; Theory: C, 47.67; H, 5.18; N,9.81; S, 7.49; Br, 18.65. Found: C, 47.87; H, 5.31; N, 10.02; S, 7.69;Br, 18.77.

EXAMPLE 147N-[5-(1,1-dimethyl-2-propenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide

M.P. 225°-228° C. Yield 52%.

Analysis calculated for C₁₉ H₁₉ N₃ O₃ S; Theory: C, 57.64; H, 5.74; N,12.60; S, 9.62. Found: C, 57.83; H, 5.91; N, 12.87; S, 9.58.

EXAMPLE 148N-(5-cycloheptyl-1,3,4-thiadiazol-2-yl)-2,6-dimethoxybenzamide

M.P. 213°-215° C. Yield 80.5%.

Analysis calculated for C₁₈ H₂₃ N₃ O₃ S; Theory: C, 59.81; H, 6.41; N,11.63; S, 8.87. Found: C, 59.91; H, 6.22; N, 11.71; S, 8.67.

EXAMPLE 149N-[5-(1-ethyl-1-methylpentyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide

M.P. 141°-143° C. Yield 48.8%.

Analysis calculated for C₁₉ H₂₇ N₃ O₃ S; Theory: C, 60.45; H, 7.21; N,11.13; S, 8.49. Found: C, 60.49; H, 7.08; N, 11.12; S, 8.29.

EXAMPLE 150N-[5-(1-ethyl-1-propylbutyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide

M.P. 216°-218° C. Yield 47.9%.

Analysis calculated for C₂₀ H₂₉ N₃ O₃ S; Theory: C, 61.35; H, 7.47; N,10.73; S, 8.19. Found: C, 61.65; H, 7.54; N, 10.46; S, 8.31.

EXAMPLE 151N-[5-(1-ethyl-1,3-dimethylbutyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide

M.P. 166°-168° C. Yield 17.6%.

Analysis calculated for C₁₉ H₂₇ N₃ O₃ S; Theory: C, 60.45; H, 7.21; N,11.13; S, 8.49. Found: C, 60.54; H, 7.21; N, 11.07; S, 8.68.

EXAMPLE 152N-[5-(1-ethyl-1-methylhexyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide

M.P. 107°-109° C. Yield 36.9%.

Analysis calculated for C₂₀ H₂₉ N₃ O₃ S; Theory: C, 61.35; H, 7.47; N,10.73; S, 8.19. Found: C, 61.53; H, 7.23; N, 10.97; S, 8.38.

EXAMPLE 153N-[5-(1-ethyl-1,2-dimethylpropyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide

M.P. 205°-207° C. Yield 48.8%.

Analysis calculated for C₁₈ H₂₅ N₃ O₃ S₁ ; Theory: C, 59.48; H, 6.93; N,11.56; S, 8.82. Found: C, 59.68; H, 7.00; N, 11.64; S, 9.04.

EXAMPLE 154N-[5-(2-methoxy-1,1-dimethylpropyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide

M.P. 202°-203° C. Yield 25%.

Analysis calculated for C₁₇ H₂₃ N₃ O₄ S; Theory: C, 55.87; H, 6.34; N,11.50; S, 8.77. Found: C, 55.87; H, 6.24; N, 11.31; S, 9.02.

EXAMPLE 155N-[5-(1-methyl-1-(methylthio)propyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide

M.P. 223°-224° C. Yield 52.4%.

Analysis calculated for C₁₆ H₂₁ N₃ O₃ S₂ ; Theory: C, 52.29; H, 5.76; N,11.43; S, 17.45. Found: C, 52.57; H, 5.87; N, 11.65; S, 17.62.

EXAMPLE 156N-[5-(1-ethyl-1,2-dimethylbutyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide

M.P. 197°-199° C. Yield 14.9%.

Analysis calculated for C₁₉ H₂₇ N₃ O₃ S; Theory: C, 60.45; H, 7.21; N,11.33; S, 8.49. Found: C, 60.28; H, 6.94; N, 10.93; S, 8.74.

EXAMPLE 157N-[6-(1-ethyl-1-methylpropyl)-pyridazin-3-yl]-2,6-dimethoxybenzamide

M.P. 145°-147° C. Yield 68%.

Analysis calculated for C₁₉ H₂₅ N₃ O₃ ; Theory: C, 66.45; H, 7.34; N,12.24. Found: C, 66.71; H, 7.55; N, 12.08.

EXAMPLE 158N-[6-(1-ethylcyclohexyl)-pyridazin-3-yl]-2,6-dimethoxybenzamide

M.P. 103°-112° C.

EXAMPLE 159N-[5-(1,1-dimethyl-2-butenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide

M.P. 204°-207° C. Yield 67%.

Analysis calculated for C₁₇ H₂₁ N₃ O₃ S; Theory: C, 58.77; H, 6.09; N,12.09; S, 9.23. Found: C, 58.90; H, 6.11; N, 12.00; S, 8.97.

EXAMPLE 160N-[5-(1-ethyl-1-methylpropyl)-1,3,4-thiadiazol-2-yl]-2,3,6-trichlorobenzamide

M.P. 220°-222° C. Yield 20%.

Analysis calculated for C₁₅ H₁₆ Cl₃ N₃ OS; Theory: C, 45.87; H, 4.11; N,10.70; S, 8.16; Cl, 27.08. Found: C, 45.72; H, 4.36; N, 10.60; S, 8.36;Cl, 27.39.

EXAMPLE 161N-[5-(2,2-dichloro-1,1-dimethylethyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide

M.P. 211°-213° C. Yield 32.7%.

Analysis calculated for C₁₅ H₁₇ Cl₂ N₃ O₃ S; Theory: C, 46.16; H, 4.39;N, 10.77; S, 8.22; Cl, 18.17. Found: C, 46.29; H, 4.47; N, 10.63; S,8.42; Cl, 18.25.

EXAMPLE 162N-[3-(1,1-dimethylethyl)-1,2,4-oxadiazol-5-yl]-2,6-dimethoxybenzamide

M.P. 207°-209° C.

Analysis calculated for C₁₅ H₁₉ N₃ O₄ ; Theory: C, 59.01; H, 6.27; N,13.76. Found: C, 59.18; H, 6.49; N, 13.85.

EXAMPLE 163N-[3-(1-ethyl-1-methylpropyl)-5-isoxazolyl]-4-chlorobenzamide

M.P. 162°-164° C. Yield 10%.

Analysis calculated for C₁₆ H₁₉ ClN₂ O₂ ; Theory: C, 62.64; H, 6.24; N,9.13. Found: C, 62.68; H, 6.42; N, 9.24.

EXAMPLE 164N-[3-(1-ethyl-1-(methoxymethyl)propyl)-5-isoxazolyl]-2,6-dimethoxybenzamide

M.P. 167°-168° C. Yield 26%.

Analysis calculated for C₁₉ H₂₆ N₂ O₅ ; Theory: C, 62.97; H, 7.23; N,7.73. Found: C, 63.23; H, 7.00; N, 7.76.

EXAMPLE 165N-[5-(2-chloro(1-chloromethyl)-1-methylethyl)-1,3,4-thiadiazole-2-yl]-2,6-dimethoxybenzamide

M.P. 228°-230° C. Yield 49.3%.

Analysis calculated for C₁₅ H₁₇ Cl₂ N₃ O₃ S; Theory: C, 46.16; H, 4.39;N, 10.77; S, 8.22; Cl, 18.17. Found: C, 46.36; H, 4.23; N, 10.79; S,8.36; Cl, 18.37.

EXAMPLE 166N-[5-(1-ethyl-1-(methylthio)propyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide

M.P. 216°-218° C. Yield 65.5%.

Analysis calculated for C₁₇ H₂₃ N₃ O₃ S₂ ; Theory: C, 53.52; H, 6.08; N,11.01; S, 16.81. Found: C, 53.75; H, 5.90; N, 10.97; S, 17.05.

EXAMPLE 167N-[5-(1-ethyl-1-[(methylthio)methyl]propyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide

M.P. 209°-211° C. Yield 30.7%.

Analysis calculated for C₁₈ H₂₅ N₃ O₃ S₂ ; Theory: C, 54.66; H, 6.37; N,10.62; S, 16.21. Found: C, 54.87; H, 6.53; N, 10.49; S, 16.47.

EXAMPLE 168N-[5-(1-methyl-1-[(methylthio)methyl]propyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide

M.P. 181°-183° C. Yield 60.7%.

Analysis calculated for C₁₇ H₂₃ N₃ O₃ S₂ ; Theory: C, 53.52; H, 6.08; N,11.01; S, 16.81. Found: C, 53.56; H, 6.33; N, 10.80; S, 16.61.

EXAMPLE 169N-[5(4)-(1,1-dimethylethyl)-2-imidazolyl]-2,6-dimethoxybenzamide (A)Preparation of 2-amino-5-(1,1-dimethylethyl)imidazole

To a stirred solution of 6.8 g of aminomethyl-(1,1-dimethylethyl)ketone,as the hydrochloride salt, in 30 ml of water were added portionwise 5.0g of cynamide. The pH of the reaction mixture was adjusted to 6.0 with1N sodium hydroxide, and then the mixture was heated to 90° C. andstirred for fifty-five minutes. The reaction mixture was next cooled toroom temperature, diluted with 100 ml. of water, and extracted severaltimes with diethyl ether. The aqueous layer was made alkaline withammonium hydroxide, and again extracted several times with diethylether.The extracts from the alkaline mixture were combined and concentrated todryness to provide a solid residue. The residue thus obtained wasdissolved in 20 ml of 6N hydrochloric acid and heated at reflux forsixteen hours. The reaction mixture was cooled, concentrated to an oilby evaporation of the solvent, and the oil was dissolved in water andmade alkaline to pH 8.5. The alkaline mixture was extracted severaltimes with diethyl ether. The etheral extracts were combined, washedwith water, dried, and the solvent was removed by evaporation underreduced pressure to provide 0.5 g of5-(1,1-dimethylethyl)-2-aminoimidazole.

NMR (DMSOd₆): δ1.17 (s, 9H, t-butyl); δ5.47 (NH₂, NH), δ6.1 (s, 1H,aromatic).

(B) A mixture of 0.5 g of the 2-aminoimidazole thus prepared and 0.72 gof 2,6-dimethoxybenzoyl chloride in 50 ml of benzene was heated atreflux for sixteen hours. The reaction mixture was then cooled and thesolvent was removed by evaporation under reduced pressure. The productwas dissolved in 25 ml of ethanol, and again the solvent was removed byevaporation under reduced pressure to provide an oil. The oil waspurified by preparative thin layer chromatography to afford 25 mg ofN-[5-(4)-(1,1-dimethylethyl)-2-imidazolyl]-2,6-dimethoxybenzamide.

M.P. 170°-173° C.

NMR (DMSOd₆) δ1.2 (s, 9H, t-butyl); δ3.74 (s, 6H, methoxy); δ6.38-7.41(m, 5H, aromatic).

EXAMPLE 170N-[5-(1-ethyl-1-methylpropyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxythiobenzamide

Example 61 describes the synthesis ofN-[5-(1-ethyl-1-methylpropyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide.Five grams of this benzamide were dissolved in 75 ml of dioxane andstirred while 4.7 g of phosphorus pentachloride were added to thereaction mixture. The solution was heated at reflux under a nitrogenatmosphere for three hours. The reaction mixture next was cooled andfiltered, and the filtrate was added to 200 ml of water. The aqueousmixture was stirred for about one hour at room temperature. Theprecipitated solid that had formed was collected by filtration and airdried to give a yellow solid. The product was identified as a mixture ofstarting material and desired product. The mixture was separated by highpressure liquid chromatography, using fifty percent ethylacetate/hexane, v/v, as the solvent. The faster moving material wascollected and identified asN-[5-(1-ethyl-1-methylpropyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxythiobenzamide.

M.P. 202°-204° C. Yield 17.6%.

Analysis calculated for C₁₇ H₂₃ N₃ O₂ S₂ ; Theory: C, 55.86; H, 6.34; N,11.50; S, 17.51. Found: C, 55.71; H, 6.51; N, 11.32; S, 17.72.

EXAMPLE 171N-[3-(1-ethyl-1-methylpropyl)-5-isoxazolyl]-2,6-dimethoxythiobenzamide

A suspension of 6.0 g ofN-[3-(1-ethyl-1-methylpropyl)-5-isoxazolyl]-2,6-dimethoxybenzamide(prepared as described in Example 1) and 7.28 g of[2,4-bis(4-methoxyphenyl)-1,3-dithia-2,4-diphosphetane-2,4-disulfide(Lawesson's Reagent) in 150 ml of toluene was heated at reflux until itturned orange color. The reaction mixture was then cooled to roomtemperature and the solvent was removed by evaporation under reducedpressure to provide a solid. The solid was suspended in dichloromethaneand filtered. The solvent was removed from the filtrate by evaporationunder reduced pressure to afford a reddish orange viscous oil. The oilwas purified by chromatography over a column of dry-packed silica gel(500 g), and the column was eluted with dichloromethane. Fractionscontaining the major component were combined and the solvent was removedby evaporation under reduced pressure to provide 4.1 g of a yellow solididentified asN-[3-(1-ethyl-1-methylpropyl)-5-isoxazolyl]-2,6-dimethoxythiobenzamide.

M.P. 110°-112° C.

Analysis calculated for C₁₈ H₂₄ N₂ O₃ S; Theory: C, 62.04; H, 6.94; N,8.04; S, 9.20. Found: C, 62.00; H, 7.09; N, 7.96; S, 8.91.

EXAMPLE 172N-[3-((2-methoxy-1-methoxymethyl)-1-methylethyl)-5-isoxazolyl]-2,6-dimethoxybenzamide

A suspension of 9.5 g of thionyl chloride in 300 ml of benzene contained7.27 g of 2,6-dimethoxybenzoic acid was heated at 65° C. for eighteenhours to provide a clear yellow solution. The solvent was removed byevaporation under reduced pressure, and 100 ml of fresh benzene wereadded, followed by the addition to the mixture of 8.6 g of3-[(2-methoxy-1-methoxymethyl)-1-methylethyl]-5-aminoisoxazole. Thereaction mixture was heated to reflux for eighteen hours, and thencooled. The solvent was removed by evaporation to provide a solid thatwas then dissolved in dichloromethane. The organic layer was extractedwith 200 ml of 1N sodium hydroxide, and the aqueous alkaline extract wascooled in an ice bath and acidified with 2N hydrochloric acid to providea solid precipitate. The aqueous mixture was extracted withdichloromethane, and the organic extract was washed with brine anddried. Evaporation of the solvent provided a white solid. The solid wascrystallized from dichloromethane and diethyl ether to give 8.42 g (77%yield) ofN-[3-((2-methoxy-1-methoxymethyl)-1-methylethyl)-5-isoxazolyl]-2,6-dimethoxybenzamide.

M.P. 164°-166° C.

Analysis calculated for C₁₈ H₂₄ N₂ O₆ ; Theory: C, 59.33; H, 6.64; N,7.69. Found: C, 59.50; H, 6.46; N, 7.63.

EXAMPLE 173N-[5-((2-acetoxy-1-acetoxymethyl)-1-methylethyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide

A solution of 300 mg of 2,6-dimethoxybenzoyl chloride in 20 ml oftoluene containing 300 mg of2-amino-5-[(2-acetoxy-1-acetoxymethyl)-1-methylethyl]-1,3,4-thiadiazolewas heated at reflux for eighteen hours. The reaction mixture was cooledto room temperature and diluted with pentane. A solid precipitate whichformed was collected by filtration and air dried to giveN-[5-((2-acetoxy-1-acetoxymethyl)-1-methylethyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamidein 3% yield.

M.P. 115°-125° C. (dec.).

EXAMPLE 174N-[3-((2-methoxy-1-methoxymethyl)-1-methylethyl)-5-isoxazolyl]-2,6-dimethoxybenzamide,sodium salt

To a stirred solution of 3.64 g ofN-[3-((2-methoxy-1-methoxymethyl)-1-methylethyl)-5-isoxazolyl]-2,6-dimethoxybenzamide(from Example 172) in 75 ml of tetrahydrofuran was added portion-wiseover five minutes 432 mg of sodium hydride. Following complete addition,the reaction mixture became slightly yellow clear solution, and then aprecipitate started to form. The mixture was cooled to 15° C., and thenfiltered. The precipitate was washed with fresh tetrahydrofuran, andthen dried at 100° C. to provide 2.25 g of hygroscopic solid identifiedasN-[3-((2-methoxy-1-methoxymethyl)-1-methylethyl)-5-isoxazolyl]-2,6-dimethoxybenzamide,sodium salt.

M.P. 82°-84° C.

Analysis calculated for C₁₈ H₂₃ N₂ O₆ Na; Theory: C, 54.68; H, 5.86; N,7.09. Found: C, 54.93; H, 6.25; N, 6.80.

EXAMPLE 175N-[3-(1-ethyl-1-methylpropyl)-5-isoxazolyl]-2,6-dimethoxybenzamide,sodium salt

A solution of 3.32 g of the benzamide of Example 1 in 20 ml ofdichloromethane and 20 ml of diethyl ether was stirred at roomtemperature under a nitrogen atmosphere while 432 mg of sodium hydridewere added portion-wise over about two minutes. A white precipitateformed as the solution was stirred. The precipitate was collected byfiltration, washed with diethyl ether and dried in a vacuum at 60° C. toprovide 2.94 g ofN-[3-(1-ethyl-1-methylpropyl)-5-isoxazolyl]-2,6-dimethoxybenzamidesodium salt.

M.P. 218°-220° C. 83% Yield.

EXAMPLE 176N-[5-(2-methyl-1,3-dithian-2-yl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide

A solution of 1.0 g of 2,6-dimethoxybenzoyl chloride in 50 ml of toluenecontaining 1.0 g of2-amino-5-(2-methyl-1,3-dithian-2-yl)-1,3,4-thiadiazole was heated atreflux for fifteen hours. The reaction mixture was then cooled to roomtemperature and diluted with pentane, whereupon a white precipitateformed. The precipitate was collected by filtration and identified asN-[5-(2-methyl-1,3-dithian-2-yl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide.

M.P. 259° C. (dec). Yield 2%.

EXAMPLE 177N-[5-(1,3-dithian-2-yl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide

A solution of 1.0 g. of 2,6-dimethoxybenzoyl chloride and 1.1 g of2-amino-5-(1,3-dithian-2-yl)-1,3,4-thiadiazole in 20 ml of toluene washeated at reflux for eighteen hours under a nitrogen atmosphere. Thereaction mixture was cooled to room temperature and the solvent wasremoved by evaporation under reduced pressure to provide a white solid.The solid was chromatographed over silica gel to provide 1.2 g (60%yield) ofN-[5-(1,3-dithian-2-yl)-1,3,4-thiadiazol-2yl]-2,6-dimethoxybenzamide.

M.P. 200°-202° C.

The benzamides provided by this invention have been found to displayuseful herbicidal activity against a variety of weed species commonlyoccuring in areas utilized for growing desired crops such as the cerealgrains and the like. The selective herbicidal activity of the compoundshas been analyzed in a number of standard greenhouse and open fieldtests. One such test was a broad spectrum greenhouse test carried out byfilling square plastic pots with a sterilized sandy loam soil andplanting seeds of tomato, large crabgrass and pigweed. Each pot wasfertilized with 158 mg of a 23-21-17 fertilizer four days beforetreatment with test compound.

The test compounds were formulated for application by dissolving eachcompound in a solution comprising 100 ml of acetone and 100 ml ofethanol plus 1.174 g of Toximul R and 0.783 g of Toximul S. (Toximul Rand Toximul S are proprietary blends of anionic and nonionic surfactantsmanufactured by Stepan Chemical Company, Northfield, Ill.). Each testcompound was dissolved in the diluent at the rate of 20 mg per 2 ml ofsolvent, and then the solution was diluted to 8 ml with deionized water.The formulated compounds were applied to the planted pots at aneffective rate of 15 pounds per acre.

Test compounds were applied postemergence to some planted pots andpreemergence to others. The postemergence applications were made byspraying the solution containing the test compound over the emergedplants about twelve days after the seeds were planted. Preemergenceapplications were sprayed on the soil one day after the seeds wereplanted.

Following application of the test compounds, the pots were placed in agreenhouse and watered as necessary. Observations were conducted about10-13 days following application of the test compounds, and untreatedcontrol plants were used as standards in each observation. The degree ofherbicidal activity of the test compounds was determined by rating thetreated plants on a scale of 1-5. On this scale, "1" indicates no plantinjury; "2" is slight injury; "3" is moderate plant injury; "4" issevere injury and "5" is death of the plant or no seedling emergence.The type of plant injury sustained by the plants was tabulated using thefollowing code letters:

A=abscission of leaves

B=burned

C=chlorosis

D=death

E=epinasty

F=formative effects

G=dark green

I=increased plant growth

L=local necrosis

N=no germination

P=purple pigmentation

R=reduced germination

S=stunting

U=unclassified injury

Compounds causing plant injuries rated 4 or 5 are considered veryactive, while compounds rated 2 or 3 are considered moderately active.

Table I below presents the herbicidal activity of typical benzamides ofthe invention when evaluated in a broad spectrum screen as describedabove.

                                      TABLE I                                     __________________________________________________________________________           Preemergence    Postemergence                                          Compound of Large           Large                                             Example No.                                                                          Tomato                                                                             Crabgrass                                                                           Pigweed                                                                            Tomato                                                                             Crabgrass                                                                           Pigweed                                     __________________________________________________________________________     1     5N   5N    5N   4BS  4BS   4BS                                          2     1    1     5N   1    1     1                                            3     4RS  3S    4RS  1    1     1                                            4     1    1     5N   5D   1     4CBS                                         5     1    1     3RS  4CBS 4BS   5D                                           9     5N   2CBS  5N   2CBS 1     1                                           10     3RS  3RS   4RS  3GS  1     1                                           14     5N   5N    5N   4BS  2BS   4BS                                         16     5N   4RS   5N   4BS  3CBS  4CBS                                        17     5N   4S    5N   3SB  2SB   3SB                                         18     2S   2S    3S   5D   2S    4SB                                         21     1    1     5N   1    1     1                                           23     5N   5N    1    2S   1     1                                           24     5N   5N    5N   4CFS 2BS   3FS                                         25     5N   5N    5N   5D   1     5D                                          29     5N   5N    5N   3FS  1     2FS                                         33     1    1     5N   1    1     1                                           37     1    5D    1    1    2CBS  1                                           54     5N   5N    5N   4CBS 1     4CBS                                        55     1    5N    5N   4FS  2S    3FS                                         57     1    4RS   4RS  1    1     1                                           58     5N   5N    5N   2FS  1     1                                           61     5N   4RS   5N   4BS  1     4BS                                         64     4RS  1     5N   2FS  1     1                                           67     1    2S    5N   1    1     1                                           69     1    1     1    1    2BS   2BS                                         71     5N   1     5N   4CBS 2PBS  4BS                                         73     4RS  2RS   4RS  4BS  2PBS  4BS                                         74     5N   5N    5N   3BS  2BS   3BS                                         75     4RS  1     5N   2CBS 1     1                                           76     5N   5N    5N   4BS  2BS   5D                                          79     3S   4S    3S   1    1     1                                           80     5N   3RS   5N   1    1     1                                           82     5N   1     5N   2CS  1     1                                           86     1    1     1    2CBS 2BS   3BS                                         90     5N   5N    5N   4CFS 2BS   3FS                                         95     5N   5N    5N   4BS  3BS   4FS                                         98     1    1     5N   1    1     1                                           99     1    1     5N   1    1     1                                           105    4RS  1     4RS  1    1     3RS                                         107    4RS  3RS   4RS  2S   2BS   2FS                                         108    3RS  2S    5N   1    1     2BS                                         109    5N   3RS   5N   4FS  2PBS  4FS                                         116    5N   4RS   4RS  3GFS 2BS   1                                           117    3RS  2RS   4RS  4BS  2BS   3BS                                         119    2CBS 2CBS  2S   4CBS 4CBS  4CBS                                        122    5N   5N    5N   4CBS 2BS   5D                                          132    1    1     1    1    1     1                                           134    1    1     1    1    1     1                                           147    2RS  1     3RS  1    1     1                                           148    1    1     1    1    1     1                                           149    4RS  4RS   5N   2FS  1     2FS                                         151    2RS  3RS   3RS  2FS  1     3CS                                         153    1    2RS   2RS  3CS  1     3CS                                         155    5N   5N    5N   2FS  1     2FS                                         157    5N   5N    5N   5D   4BS   5D                                          161    5N   5N    5N   1    1     1                                           169    5N   5N    5N   3CBS 1     2CS                                         170    4RS  4RS   5N   1    1     1                                           __________________________________________________________________________

A similar greenhouse study utilizing seven seed species was carried outto further evaluate preemergence and postemergence herbicidal activityof the benzamides of this invention. The compounds to be evaluated wereformulated according to the procedure outlined above, except that about4 g/100 ml of the compound were dissolved in the surfactant-containingsolvent, and about 1 part of the organic solution was diluted with 12parts of water before application to seeded containers. The compoundswere applied at the effective rate of 8 lbs/acre. Typical results ofsuch evaluation are presented in Table II below.

                                      TABLE II                                    __________________________________________________________________________    Compound                                                                            Preemergence             Postemergence                                  of       Large         Morn-      Large         Morn-                         Example  Crab-                                                                             Pig-                                                                             Fox-                                                                             Velvet                                                                            ing-       Crab-                                                                             Pig-                                                                             Fox-                                                                             Velvet                                                                            ing-                          Number                                                                              Corn                                                                             grass                                                                             weed                                                                             tail                                                                             Leaf                                                                              glory                                                                             Zinnia                                                                            Corn                                                                             grass                                                                             weed                                                                             tail                                                                             Leaf                                                                              glory                                                                             Zinnia                    __________________________________________________________________________     1    5  5   5  5  5   4   5   1  3   3  2  1   2   3                          2    1  1   4  1  1   2   3   1  1   1  1  1   1   2                          4    1  2   5  2  2   3   5   1  1   1  1  1   1   1                          6    1  1   5  1  1   1   2   2  1   1  1  1   1   2                          8    1  1   3  1  1   2   1   1  1   1  1  1   1   1                          9    3  4   5  4  1   1   4   1  1   1  1  1   1   1                         10    2  5   5  3  3   2   4   1  1   3  1  1   2   3                         11    1  3   5  2  1   2   1   1  1   2  1  1   1   3                         12    2  4   5  3  3   3   2   2  1   3  1  2   2   3                         13    3  4   5  4  1   1   1   1  1   3  1  1   2   2                         14    4  5   5  5  4   5   5   2  1   4  1  2   3   3                         16    3  4   5  4  3   3   3   2  1   1  1  1   2   3                         17    2  4   5  4  3   2   2   2  1   3  2  2   2   3                         19    5  5   5  5  5   5   5   3  3   4  2  3   3   3                         22    3  4   5  2  2   4   4   1  1   3  1  1   2   3                         23    2  5   5  4  3   3   3   1  1   3  1  1   1   2                         24    3  4   5  3  3   3   5   1  1   2  1  2   1   2                         26    1  3   5  2  2   1   3   1  1   2  1  1   1   2                         30    2  1   1  2  1   1   2   1  1   1  1  1   1   1                         33    1  1   2  1  3   1   5   1  1   1  1  1   1   1                         37    2  3   2  2  1   1   1   2  1   1  1  2   2   2                         41    1  1   4  1  1   1   1   1  1   3  1  1   1   3                         47    2  1   1  3  2   1   3   1  1   1  1  1   1   1                         48    1  2   2  2  1   1   1   1  1   1  1  1   1   1                         49    1  3   2  2  1   1   1   -- --  -- -- --  --  --                        50    1  1   2  1  1   1   1   1  1   1  1  1   1   1                         51    1  1   1  1  1   1   1   1  1   1  1  1   2   2                         52    1  1   1  1  1   2   1   2  1   1  1  1   1   1                         53    2  1   1  1  1   1   1   2  1   1  1  1   1   1                         54    2  1   1  1  1   1   1   2  1   1  1  2   2   2                         55    2  5   5  5  5   3   3   1  2   4  1  3   2   3                         56    2  5   5  5  4   5   5   1  3   3  2  1   2   1                         57    1  1   2  2  1   1   1   1  1   1  1  1   1   1                         58    1  1   3  1  1   1   3   1  1   1  1  1   1   1                         59    1  1   3  1  1   1   1   1  1   1  1  1   1   1                         61    4  5   5  5  5   5   5   2  2   4  1  1   2   3                         62    1  3   5  2  2   1   2   2  3   4  1  2   1   1                         63    1  2   4  1  1   2   3   1  1   2  1  1   2   2                         64    1  2   5  1  1   2   2   1  1   2  1  1   1   2                         66    3  4   5  4  3   2   3   2  1   3  1  1   2   2                         67    1  3   5  2  1   2   2   1  1   1  1  1   1   1                         68    1  2   5  2  2   2   5   1  1   3  1  1   1   2                         69    1  1   2  1  1   2   2   1  1   3  1  1   2   2                         70    1  1   1  1  1   1   1   1  2   2  1  1   1   1                         75    1  1   4  1  1   1   3   1  1   1  1  1   2   1                         77    1  1   2  1  1   1   1   1  1   1  1  1   1   1                         78    1  1   3  1  1   1   1   1  1   1  1  1   1   1                         79    1  1   1  1  1   2   1   1  1   1  1  2   2   2                         80    1  4   5  3  1   2   5   2  1   1  1  1   2   2                         81    1  1   3  1  1   1   1   1  1   1  1  1   1   1                         82    1  4   5  2  2   3   4   1  1   3  1  1   1   1                         83    2  4   5  3  2   3   4   1  1   1  1  1   1   1                         84    1  1   4  1  1   1   1   1  1   1  1  1   1   1                         85    1  1   1  1  1   1   1   1  1   1  1  1   1   1                         86    1  1   4  1  1   1   1   1  1   1  1  1   1   1                         87    1  3   3  2  3   2   3   1  1   1  1  1   1   1                         88    3  5   5  4  3   3   3   1  1   3  1  1   1   2                         92    1  1   3  1  1   1   1   1  1   1  1  1   2   1                         94    1  1   1  1  1   1   1   1  1   1  1  1   1   1                         95    3  4   5  4  3   3   2   1  2   4  2  3   3   3                         97    1  3   5  2  1   1   3   1  1   1  1  1   1   1                         99    1  4   5  1  1   1   1   1  1   3  1  1   1   2                         100   1  1   1  1  1   1   1   1  1   1  1  2   2   1                         101   1  4   4  1  1   3   2   2  1   2  1  1   1   2                         102   1  2   3  1  1   1   2   1  1   1  1  1   1   1                         103   1  4   1  1  1   1   1   2  1   3  1  1   3   5                         104   1  4   3  3  2   2   1   1  1   1  1  1   2   1                         106   1  1   1  1  1   1   1   1  1   1  1  1   1   2                         110   1  1   1  1  1   1   1   1  1   1  1  1   1   1                         113   2  1   2  1  1   1   1   2  1   1  1  1   1   1                         114   1  4   5  3  2   3   5   1  1   1  1  1   1   1                         115   2  4   4  3  2   4   3   1  1   1  2  1   1   2                         116   1  4   4  2  2   2   1   1  1   1  1  1   1   2                         118   1  2   5  1  2   2   2   1  1   1  1  1   1   1                         119   1  2   2  4  3   1   3   1  2   3  3  2   1   1                         126   1  2   2  1  1   1   1   1  1   1  1  1   1   1                         128   1  5   4  1  3   2   2   1  1   3  1  1   1   2                         129   1  1   2  1  1   1   1   1  1   1  1  1   1   1                         131   1  1   1  1  1   1   1   1  1   1  1  1   1   1                         137   1  1   1  1  1   1   1   1  3   1  1  1   1   2                         138   1  2   2  1  1   1   1   1  1   1  1  1   1   1                         139   1  1   2  1  1   1   1   1  1   1  1  1   1   1                         140   1  1   4  2  1   1   2   1  1   1  1  1   1   1                         141   3  5   5  5  5   5   5   2  2   2  2  2   3   2                         142   2  3   3  4  5   5   4   1  1   1  1  1   1   1                         143   1  1   1  1  1   1   1   1  1   1  1  1   1   1                         144   2  1   4  1  1   1   1   1  1   1  1  1   2   1                         145   1  4   5  3  1   1   1   1  1   1  1  1   1   1                         146   1  1   2  1  1   1   2   1  1   1  1  1   1   1                         150   1  1   1  1  1   1   1   1  2   1  1  1   2   2                         152   2  4   5  4  2   4   2   1  2   4  2  3   2   3                         154   1  2   2  1  1   2   2   1  1   2  1  1   2   2                         156   1  4   5  1  1   3   2   1  1   3  1  1   1   1                         158   3  5   5  3  3   4   3   2  2   3  2  2   3   4                         162   1  2   2  1  1   1   1   1  1   1  1  1   1   1                         163   1  1   1  1  1   1   1   1  1   2  1  1   1   1                         166   4  3   4  5  5   3   1   2  1   1  1  1   1   1                         167   1  3   5  3  1   2   2   1  1   1  1  1   1   1                         168   5  5   4  5  3   4   2   4  3   2  1  1   2   1                         170   3  4   5  3  2   2   2   1  1   1  1  1   1   1                         173   1  2   4  1  2   1   1   1  1   1  1  1   1   1                         176   1  4   5  2  2   1   1   1  1   1  1  1   1   1                         __________________________________________________________________________

The herbicidal activity of a number of the more active benzamides of theinvention was evaluated at various application rates in amultiple-species greenhouse test. Several additional weed and cropspecies were utilized to determine the herbicidal selectivity of thecompounds. The compounds were formulated as described above, and appliedpreemergence to seeded flats. The results for several compounds of theinvention are presented below in Table III.

    TABLE III      Compound  Preemergence of Rate of          Barn-  Large         Example     Application  Cot- Soy-   Sugar    yard Lambs- Crab- Mus-     Jimson     Morning- No. Lbs/Acre Corn ton bean Wheat Alfalfa Beat Rice Cucumber     Tomato Grass quarter grass tard Pigweed Foxtail Wildoat Velvetleaf Weed     glory Zinnia       1 1 4 1 4 1 2 5 3 5 5 5 5 5 5 5 5 3 4 5 3 5  0.5 2 1 3 1 5 5 3 2 5 4 5     5 5 5 5 2 3 5 2 5  0.25 1 1 2 1 5 5 5 4 4 4 5 5 5 5 4 1 2 5 2 3 3 1 1 1     2 1 1 5 2 3 4 4 5 4 3 4 1 1 3 1 1 2  0.5 1 1 1 1 1 5 1 2 3 3 5 3 3 4 1 1     2 1 1 2  0.25 1 1 1 1 1 5 1 1 1 1 4 1 2 5 1 1 2 1 1 2 4 1 1 1 1 1 4 5 1     1 2 1 5 1 4 5 1 1 1 4 1 5  0.5 1 1 1 1 4 5 1 1 3 1 5 1 3 4 1 1 1 4 1 4     0.25 1 1 1 1 1 4 1 1 1 1 5 1 2 3 2 1 1 3 1 1 5 4 1 1 1 1 1 5 1 1 1 2 5 1     2 5 1 1 1 3 1 1  1 1 1 1 1 1 3 1 1 1 1 5 1 1 3 1 1 1 2 2 2 6 4 2 2 4 3 4     5 1 2 4 1 5 2 5 5 4 1 2 5 4 5  2 2 2 2 1 2 5 1 1 4 1 5 1 3 5 1 1 1 4 1 5      1 1 1 2 1 1 4 1 2 4 1 5 1 3 4 1 1 1 2 1 4  0.5 1 1 2 1 1 3 1 2 1 1 5 1     3 2 1 1 2 1 1 3  0.25 1 1 1 1 1 4 1 1 1 1 5 1 3 2 1 1 1 2 1 2 9 4 2 1 3     1 3 5 2 2 4 4 5 3 5 5 3 1 2 5 3 5  1 1 1 2 1 2 5 2 2 2 3 5 3 5 5 2 1 1 4     2 4  0.5 1 1 1 1 2 5 2 1 2 3 5 2 4 5 1 1 2 3 1 3  0.125 1 1 1 1 1 5 1 1     1 1 5 1 1 5 1 1 1 1 1 1 11 4 1 1 1 1 1 3 1 1 1 1 3 1 4 3 2 1 1 2 1 2  2     1 1 1 1 1 2 1 2 1 2 5 1 4 3 1 1 1 2 1 2  1 1 1 1 1 1 1 1 1 1 1 4 1 3 2 1     1 1 1 1 1 13 4 2 1 2 1 1 4 1 3 1 3 5 3 2 3 2 1 1 1 1 1  2 1 1 2 1 1 4 1     2 2 2 4 3 1 2 2 1 1 3 1 1  1 1 1 1 1 1 3 1 1 2 1 3 1 1 1 1 1 1 1 1 1 14     1 2 2 3 1 5 5 2 5 5 5 5 5 5 5 5 1 3 5 3 4  0.5 2 1 2 1 1 3 1 2 3 3 5 3 4     3 4 1 2 3 2 4  0.25 1 1 2 1 2 2 3 1 2 3 5 3 5 2 2 1 2 4 1 2 15 1 1 1 1 1     1 3 1 1 4 3 5 2 5 4 1 1 2 4 2 5  0.5 1 1 1 1 1 4 1 2 4 1 5 2 4 3 1 1 2 2     1 2  0.25 1 1 1 1 1 3 1 1 5 1 5 1 4 5 1 1 2 5 1 2 16 1 1 1 2 1 3 5 1 3 5     4 5 4 5 5 4 1 2 5 1 4  0.5 1 1 2 1 5 5 1 1 2 2 5 1 4 5 1 1 1 5 1 2  0.25     1 1 1 1 4 4 1 1 1 1 5 1 4 5 1 1 1 2 1 1 17 1 1 2 3 2 3 5 1 1 5 4 5 4 4 4     2 2 2 3 2 1  0.5 2 1 3 1 3 3 1 3 4 3 5 4 5 5 2 2 3 2 2 1  0.25 2 2 3 2 5     5 1 1 1 3 5 4 3 4 1 1 1 2 1 1 21 1 1 1 -- 1 1 2 1 3 2 2 5 2 3 5 1 1 1 2     1 1  0.5 1 2 -- 1 2 5 1 1 1 1 5 1 1 2 1 1 1 1 1 1  0.25 1 1 -- 1 1 1 1 1     1 1 4 1 1 2 1 1 1 1 1 1 23 1 1 1 2 1 1 5 3 3 5 5 5 5 4 4 4 2 2 -- 3 3     0.5 2 1 1 1 1 5 1 3 5 4 5 3 3 3 3 2 3 -- 1 2  0.25 2 1 1 1 1 5 2 2 3 4 5     3 2 2 2 2 1 -- 1 2  0.125 1 1 1 1 1 5 1 1 1 1 5 4 2 5 3 1 2 2 2 4 24 1 1     1 1 1 1 4 1 1 1 1 5 1 3 4 1 1 1 3 1 4  0.5 1 1 1 1 1 4 1 3 2 1 5 2 4 4 1     1 1 -- 1 4  0.25 1 2 1 1 1 3 1 2 2 1 5 2 3 5 2 1 1 -- 1 4 26 4 1 2 2 1 1     5 1 1 1 1 5 2 4 3 1 1 1 1 1 2  2 1 1 1 1 1 4 1 1 1 1 5 2 3 2 1 1 1 2 1 2      1 1 1 1 1 1 2 1 1 1 1 2 2 3 1 1 1 1 1 1 2 27 4 1 2 3 1 3 5 2 4 4 2 5 1     5 5 2 1 2 4 2 5  2 1 1 4 1 3 5 1 2 4 1 5 1 5 5 1 1 2 5 3 3  1 1 1 1 1 5     5 1 2 3 1 5 1 5 5 1 1 1 2 2 5  0.5 1 1 2 1 4 4 1 3 1 1 5 1 3 4 1 1 2 3 1     4 29 1 2 1 1 1 1 5 2 4 2 4 5 4 3 4 3 2 3 2 1 2  0.5 2 1 1 1 1 2 1 3 1 3     5 3 2 4 2 2 3 2 1 2  0.25 2 1 1 1 1 2 1 2 1 3 4 3 2 3 1 2 2 1 1 1 31 1 1     1 2 1 1 4 1 2 1 2 4 2 2 3 1 1 1 3 1 1  0.5 1 1 1 1 1 4 1 1 1 1 2 1 1 3 1     1 1 1 1 1  0.25 1 1 1 1 1 1 1 1 1 1 1 1 2 2 1 1 1 1 1 1 33 2 1 1 1 1 1 4     1 1 1 1 4 1 2 3 2 1 1 1 1 1  1 1 1 1 1 1 3 1 1 1 1 4 1 1 2 1 1 1 1 1 1     34 1 2 1 3 1 2 4 1 1 1 2 5 4 2 4 4 1 3 3 2 2  0.5 1 1 1 1 1 3 1 1 1 2 5     4 2 3 1 1 1 1 2 3 35 1 1 1 1 1 1 2 1 1 1 1 5 1 1 4 1 1 2 1 1 1  0.5 1 1     1 1 1 1 1 1 1 1 2 1 1 3 1 1 1 1 1 1 36 1 1 1 1 1 1 4 1 1 1 1 1 1 1 2 1 1     1 1 1 1  0.5 1 1 1 1 1 3 1 1 1 1 1 1 1 1 1 1 1 1 1 1 42 1 1 1 1 1 1 4 2     2 2 1 5 2 4 3 1 1 1 1 1 2  0.5 1 1 1 1 1 4 1 1 1 1 5 1 1 3 1 1 1 1 1 3     43 4 1 1 1 1 1 4 1 2 1 1 5 3 1 4 2 1 1 1 1 1  2 1 1 1 1 1 2 1 1 1 1 4 3     2 4 1 1 1 1 1 1 61 4 4 1 4 3 5 5 4 5 5 5 5 5 5 5 5 4 5 5 3 5  0.5 2 1 4     2 4 5 3 2 2 3 5 4 4 5 4 1 2 4 2 3  0.125 1 1 1 1 4 2 1 2 1 1 5 3 4 5 1 1     2 2 1 2 62 4 2 1 2 1 1 1 1 1 1 1 4 2 1 3 1 1 2 3 1 1  2 1 1 1 1 1 1 1 1     1 1 2 2 1 2 1 1 1 2 1 1  1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 63 1     1 1 1 1 1 1 1 1 1 1 4 1 3 4 1 1 1 1 1 1  0.5 1 1 1 1 1 1 1 2 1 2 1 1 1 4     1 1 1 2 1 1  0.25 1 1 1 1 1 1 1 1 1 1 1 1 1 4 1 1 1 1 1 1 64 4 1 1 1 1 1     4 -- 2 2 2 5 1 3 4 2 1 1 3 2 4  2 1 1 1 1 1 3 1 1 2 1 5 1 2 3 1 1 1 3 1     2  1 1 1 1 1 1 1 1 2 1 1 3 2 3 3 1 1 2 1 1 1 66 4 4 2 4 2 5 5 4 3 5 5 5     5 5 5 5 2 4 5 3 3  1 2 2 3 2 3 5 3 2 2 4 5 4 3 5 4 2 2 1 1 3  0.5 2 1 3     1 1 5 4 2 2 4 5 4 4 4 4 2 3 5 2 2  0.125 1 2 1 1 1 2 1 2 1 1 5 3 2 5 1 1     1 1 1 1 68 4 1 1 1 1 1 4 2 2 2 2 5 2 4 5 1 1 1 3 1 3  2 1 1 1 1 1 4 1 1     1 1 5 1 3 3 1 1 1 2 1 2  1 1 1 1 1 1 4 1 1 3 1 5 1 4 4 1 1 1 2 1 2  0.5     1 1 1 1 1 1 1 1 1 1 5 1 2 4 1 1 1 1 1 2 73 4 1 2 3 1 3 3 1 3 3 3 5 4 5 5     2 2 1 5 2 4  1 1 1 2 1 1 4 2 1 2 2 5 2 5 5 1 1 1 5 1 1  0.5 1 1 1 1 1 1     1 1 3 1 5 1 3 5 1 1 1 3 1 1 74 1 1 1 2 1 3 5 3 2 3 3 5 3 3 5 2 3 3 4 2 1      0.5 1 1 2 1 2 5 4 1 1 3 5 4 3 5 2 1 1 5 1 2  0.25 2 1 1 1 1 5 1 1 5 2 5     1 2 5 1 1 1 4 1 1 76 1 1 1 2 2 4 4 1 2 5 5 5 5 5 5 4 2 2 4 2 3  0.5 1 1     1 1 1 2 2 3 2 1 5 3 3 4 1 1 2 4 1 2  0.25 1 1 1 1 1 2 1 1 3 1 4 1 3 2 1     1 1 3 1 1 83 1 1 1 1 1 4 4 1 1 2 2 5 1 3 5 1 1 1 5 1 3  0.5 1 1 1 1 1 2     1 1 1 1 5 2 3 4 1 1 1 4 1 2  0.25 1 1 1 1 1 2 1 1 1 1 5 2 2 3 1 1 1 1 1     1 89 4 1 1 -- 1 1 1 -- 2 1 1 4 1 2 3 1 1 1 -- 1 1  2 1 1 -- 1 1 1 1 1 1     1 5 1 2 5 1 1 1 -- 1 1  1 1 1 -- 1 1 1 2 1 1 1 1 1 1 4 1 1 1 -- 1 1 96 4     1 1 1 1 3 5 1 2 2 4 4 4 3 5 2 2 5 3 3 3  2 2 1 1 1 3 5 1 2 1 4 3 4 3 4 2     2 2 2 1 2  1 1 1 1 1 1 5 1 2 1 5 3 4 3 5 2 2 2 2 1 2  0.5 1 1 3 1 2 4 1     2 1 3 5 3 4 4 2 2 2 3 2 2  0.25 1 1 1 1 1 2 1 2 1 1 4 1 2 3 1 1 1 3 1 2     97 4 1 1 1 1 1 1 1 1 1 1 3 1 1 3 1 1 1 1 1 1  2 1 1 1 1 1 1 1 1 1 1 2 1     1 3 1 1 1 1 1 1  1 1 1 1 1 1 1 1 1 1 1 1 1 1 3 1 1 1 1 1 1 98 1 1 1 2 1     1 5 1 1 2 1 5 1 2 5 1 1 1 3 1 2  0.5 1 1 1 1 1 4 1 1 1 1 5 2 2 4 1 1 1 3     1 2  0.25 1 1 1 1 1 3 1 1 1 1 4 1 2 2 1 1 1 1 1 2 104 1 1 1 1 1 1 1 1 1     1 1 5 1 2 5 1 1 1 1 1 1  0.5 1 1 1 1 1 1 1 1 1 1 3 1 1 3 1 1 1 1 1 1     0.25 1 1 1 1 1 1 1 1 1 1 2 1 1 3 1 1 2 1 1 1 111 4 1 1 1 1 4 5 1 1 5 1 5     1 5 5 2 1 1 5 1 5  2 1 1 1 1 4 5 1 1 3 1 5 1 5 5 1 1 1 5 1 2  1 1 1 1 1     2 5 1 1 4 1 5 1 5 5 1 1 1 4 1 1 112 1 1 1 2 1 3 4 1 1 2 4 5 5 5 5 2 3 2     5 2 1  0.5 1 1 2 1 1 2 1 1 3 4 5 1 2 5 1 1 1 1 1 1  0.25 1 1 1 1 1 1 3 1     1 2 5 3 3 5 1 2 1 3 1 1 114 2 1 1 1 1 -- 5 1 2 2 1 5 1 3 3 1 1 1 -- 1 2     1 1 1 -- 1 1 4 1 2 3 1 5 1 3 5 1 2 1 -- 1 2  0.5 1 1 -- 1 1 4 1 3 1 1 4     1 2 3 1 1 1 2 1 2  0.25 1 1 -- 1 1 1 1 1 1 1 3 1 1 2 1 1 1 1 1 1 115 4 1     1 -- 1 1 5 1 1 3 2 5 2 1 3 3 1 1 -- 1 1  2 1 1 1 1 1 1 1 1 1 1 4 1 1 1 1     1 1 -- 1 2  1 1 1 -- 1 1 1 1 1 1 1 3 1 2 1 1 1 1 -- 1 1 116 2 1 1 2 1 4     3 1 2 4 1 5 2 4 4 3 2 2 5 3 5  1 1 1 1 1 5 4 1 1 3 1 3 3 3 3 1 1 1 -- 1     2  0.5 1 1 1 1 2 2 1 1 1 1 1 3 2 1 1 1 1 -- 1 3  0.25 1 1 1 1 1 1 1 1 2     1 3 1 2 2 1 3 1 -- 2 1 118 1 1 1 2 1 4 5 2 2 1 1 5 2 3 5 1 1 2 1 1 4     0.5 1 1 1 1 4 4 2 2 1 1 5 1 2 5 1 1 1 1 1 1  0.25 1 1 1 1 1 4 1 1 1 1 5     1 1 2 1 1 1 1 1 1 120 8 1 -- -- -- -- -- -- -- -- -- -- 4 -- 2 3 -- 4 --     2 4  4 1 1 1 1 1 1 1 1 1 1 1 1 1 2 1 1 1 1 1 2  2 1 1 1 1 1 1 1 1 1 1 1     1 1 2 1 1 1 1 1 1 123 1 1 1 1 1 3 2 1 1 1 1 5 1 4 5 1 1 1 1 1 1  0.5 1 1     1 1 1 2 1 1 1 1 5 1 3 5 1 1 1 1 1 1  0.25 1 1 1 1 1 1 1 1 1 1 3 1 1 2 1     1 1 1 1 1 124 1 1 1 1 1 1 4 1 1 1 3 5 1 3 5 1 1 1 1 1 1  0.5 1 1 1 1 1 1     1 1 1 1 5 1 1 3 1 1 1 1 1 1 125 1 1 1 3 1 2 4 1 3 4 2 5 5 4 4 4 1 3 4 1     1  0.5 1 2 2 1 1 3 1 3 2 1 5 3 3 5 4 1 1 1 1 1 127 2 1 2 4 1 1 2 1 1 3 4     4 4 4 4 2 1 1 3 1 1  1 1 1 2 1 1 1 1 1 3 3 5 4 5 5 3 1 2 2 1 1 145 2 1 1     1 1 5 5 2 3 3 4 5 1 5 5 1 1 1 4 1 3  1 1 1 1 1 5 5 1 1 1 1 5 1 2 5 1 1 1     1 1 1 149 2 2 1 1 1 1 4 2 1 4 4 5 5 3 5 4 2 2 5 1 1  1 1 1 2 1 1 5 2 1 4     4 5 5 3 5 4 2 1 4 1 1 151 2 2 1 2 1 1 4 1 1 4 5 5 5 4 5 4 1 1 3 1 1  1 2     1 1 1 1 5 2 1 5 3 5 4 5 5 4 1 3 5 2 2 153 2 1 1 3 2 4 2 1 2 2 2 4 4 2 5     2 1 3 1 3 3  1 1 1 2 1 4 2 1 1 1 2 4 4 3 5 1 1 3 1 2 2 155 2 2 2 3 1 3 5     4 5 5 5 5 5 5 5 5 1 3 5 3 3  1 1 1 1 1 1 3 1 1 3 1 5 4 5 5 4 1 1 4 1 3     157 4 5 3 5 5 5 5 4 5 5 5 5 5 5 5 5 5 5 5 5 2  1 4 2 4 4 5 5 4 5 5 5 5 5     5 4 5 5 5 5 5 4  0.25 3 1 3 2 5 5 3 5 5 5 5 5 4 5 4 4 4 4 2 3  0.125 3 1     4 3 5 5 2 3 5 5 5 4 4 5 3 3 3 4 1 2 164 4 2 2 5 2 4 5 3 5 5 3 5 5 5 5 5     3 4 5 4 4  2 1 1 5 2 5 4 2 5 4 3 5 4 5 5 4 2 5 5 2 3  1 1 1 4 2 5 4 2 5     4 2 5 3 5 5 4 1 5 5 3 2 170 4 1 1 1 1 1 2 1 1 3 4 2 4 3 4 3 1 2 4 2 3  2     1 1 1 1 1 2 1 1 2 4 5 3 2 4 1 1 2 3 1 1  1 1 1 1 1 1 2 1 1  4 5 3 3 5 4     1 2 5 2 2 176 1 1 1 1 1 1 4 1 1 2 2 5 2 4 5 1 1 1 4 1 3  0.5 1 1 1 1 1 1     1 1 1 1 5 1 1 4 1 1 1 4 2 3  0.25 1 1 1 1 1 1 1 1 1 1 4 1 2 2 1 1 1 1 1     1

As pointed out earlier, most of the compounds provided by this inventionare potent herbicidal agents when applied at low rates to soil or plantsurfaces pre- or post-emergence. Many of the compounds are even morepotent when applied to soil and incorporated therein prior to plantingof crop seeds. Pre-plant incorporation is particularly preferred whenemploying a benzamide which displays less than desirable potency orselectivity when surface applied. For example, the compound of Example52, namely N-[3-(1-methylethyl)-5-isoxazolyl]-2,6-dimethoxybenzamide,failed to retard the vigor of tomato, large crabgrass or pigweed whenapplied both pre- and post-emergence at 15 pounds per acre. When thecompound was applied at 15 pounds per acre and incorporated into thesoil prior to seeding, it totally retarded the growth of tomato, wildmustard and lambsquarter, and demonstrated significant herbicidalactivity against pigweed, sugarbeets and Jimson-weed.

The herbicidal activity of several compounds provided herein has beendetermined following pre-plant incorporation of the benzamide. Theevaluations were carried out by first formulating an appropriate amountof test compound in 2.5 ml. of a fifty percent mixture of acetone andethanol. The solution was diluted to 12.5 ml. by the addition ofdeionized water. The formulated test compound was sprayed onto fivequarts of screened, autoclaved greenhouse potting soil. The testcompound was incorporated into the soil mixture by tumbling the mixturein a modified cement mixer. The treated soil was transferred togreenhouse flats, and the flats were seeded to various weed and cropspecies. The seeded flats were maintained in a greenhouse, withsub-irrigation as needed. Plant injury ratings attributable to the testcompound were made sixteen days post treatment and planting, utilizing ascale of 0 to 10, wherein 0 is no injury and 10 represents death of theplant species. The results of typical pre-plant soil incorporationstudies are presented below in Table IV.

                                      TABLE IV                                    __________________________________________________________________________    Pre-plant soil incorporation                                                         Rate of                                                                Compound of                                                                          application    Wild Lambs-                                             Example No.                                                                          lbs/Acre                                                                            Alfalfa                                                                           Pigweed                                                                            Mustard                                                                            quarter                                                                           Sugarbeets                                                                          Tomatoes                                                                            Jimsonweed                         __________________________________________________________________________    46     15    0   5    8    8   6     6     5                                  48     15    0   5    10   10  6     5     0                                  52     15    0   6    10   10  7     10    5                                  65     15    6   10   10   10  6     6     5                                  78     15    6   10   10   10  10    5     3                                  85     8     0   4    10   9   4     5     2                                  100    15    2   8    10   10  9     8     6                                  106    15    7   10   10   10  8     6     6                                  110    15    0   9    10   8   8     10    9                                  121    4     0   3    10   6   3     3     0                                  133    8     0   7    10   10  4     3     1                                  135    15    0   9    10   10  9     8     5                                  136    15    0   2    10   6   4     6     0                                  __________________________________________________________________________

Several of the preferred benzamides of the invention have been evaluatedin a number of open field studies to determine efficacy, selectivity andcrop tolerances. In a typical field trial, the benzamides were appliedpre-emergence as an aqueous spray in soil seeded to cereal grains andhaving weed species present that are common with such crops. The studiesroutinely involved randomized blocks with four replicates. Observationswere made for grain crop vigor, weed control, crop injury, cropemergence, and root injury.

One such field study was carried out in Great Britain to determine theefficacy and selectivity of preferred benzamides when surface appliedpre-emergence to soil seeded to common wheat. Observations were madetwenty-five days post-application to determine the vigor of the treatedwheat plants compared to untreated controls, and to determine the amountof control of various weed species effected by the benzamides. Theresults of the field test are presented below in Table V. The datapresented for crop vigor is the comparison of treated wheat to untreatedwheat, the untreated controls being assigned a vigor rating of 100percent. Weed control ratings are given in percentage of controlcompared to untreated control plots based upon visual inspection.

                                      TABLE V                                     __________________________________________________________________________                                Catchweed                                                                           Wild  Ladys-                                            Rate                                                                              Crop Vigor                                                                          Blackgrass                                                                          Bedstraw                                                                            Chomomile                                                                           thumb                                                                              Chickweed                        Compound Applied                                                                          Kg/ha                                                                             Rating                                                                              Control                                                                             Control                                                                             Control                                                                             Control                                                                            Control                          __________________________________________________________________________    N--[3-(1-ethyl-1-methyl-                                                                  0.25                                                                              96    40    20    100    91  100                              butyl)-5-isoxazolyl]-                                                                     0.50                                                                              93    68    8     100   100  100                              2,6-dimethoxybenzamide                                                                    0.75                                                                              96    53    5     100   100  100                              (Compound of Ex. 14)                                                                      1.0 93    73    27    100   100  100                              N--[3-(1-methylcyclo-                                                                     0.25                                                                              97    56    0     100   100  100                              hexyl)-5-isoxazolyl]-                                                                     0.50                                                                              98    59    3     100   100  100                              2,6-dimethoxybenzamide                                                                    0.75                                                                              94    61    3     100   100  100                              (Compound of Ex. 17)                                                                      1.0 93    54    5     100   100  100                              N--[3-(1-ethylcyclo-                                                                      0.25                                                                              96    83    18    100    94  100                              hexyl)-5-isoxazolyl]-                                                                     0.50                                                                              97    55    28    100    98  100                              2,6-dimethoxybenzamide                                                                    0.75                                                                              96    83    25    100   100  100                              (Compound of Ex. 19)                                                                      1.0 93    84    63    100   100  100                              N--[3-(1,1-dimethyl-                                                                      1.0 96    60    10    100    83  100                              ethyl)-5-isoxazolyl]-                                                         2,6-dimethoxybenzamide                                                        (Compound of Ex. 6)                                                           N--[3-(1-ethyl-1-methyl-                                                                  1.0 92    66    93    100   100  100                              propyl)-5-isoxazolyl]-                                                        2,6-dimethoxybenzamide                                                        (Compound of Ex. 1)                                                           Untreated control                                                                             100    0    0      0     0    0                               __________________________________________________________________________

A field study was carried out in Brazil to evaluate the herbicidalactivity and crop tolerances of certain preferred benzamides compared tountreated controls and to commercial herbicides trifluralin andmetribuzin. The herbicides were applied as an aqueous spray and werepre-plant incorporated with a disc and harrow. Treated and untreatedplots were individually seeded to peanuts, soybeans, cotton and corn.Observations were then made sixteen and thirty-six days post-treatment.Treated plots were visually compared with untreated controls todetermine percent of crop emergence, percent of crop injury, percent ofcrop stand, and percent of root injury. Table VI which follows presentsthe effects of various herbicides on crops. Table VII presents thedegree to which the various herbicides controlled weed species commonlyencountered in the indicated crops.

                                      TABLE VI                                    __________________________________________________________________________    Compound                                                                      of        % Crop                                                                              % Crop                                                                             % Crop                                                                             % Crop                                              Example                                                                             Rate                                                                              Emergence                                                                           Injury at                                                                          Injury at                                                                          Stand at                                                                           % Root Injury                                  No.   kg/ha                                                                             at 16 Days                                                                          16 Days                                                                            36 Days                                                                            16 Days                                                                            at 36 Days                                     __________________________________________________________________________    Peanuts                                                                        1    0.13                                                                              93    7    17   101  0                                                    0.25                                                                              83    20   27   87   0                                                    0.50                                                                              70    37   37   82   40                                                   1.0 70    40   53   83   23                                              6    1.0 73    20   3    83   0                                                    2.0 83    13   13   90   10                                             28    0.13                                                                              83    20   13   92   0                                                    0.25                                                                              93    13   17   102  0                                                    0.50                                                                              83    17   20   92   0                                                    1.0 80    30   30   105  10                                             61    0.13                                                                              93    7    0    92   0                                                    0.25                                                                              87    13   13   98   0                                                    0.50                                                                              77    17   20   84   0                                                    1.0 67    37   40   80   28                                             Trifluralin                                                                         0.96                                                                              80    27   20   80   0                                              Metribuzin                                                                          0.49                                                                              77    50   47   92   0                                              Untreated 100   0    0    100  0                                              Control                                                                       Soybeans                                                                       1    0.13                                                                              53    37   30   51   0                                                    0.25                                                                              43    47   33   42   0                                                    0.50                                                                              37    57   53   26   0                                                    1.0 13    87   77   7    0                                               6    1.0 93    7    3    88   0                                                    2.0 97    0    0    103  0                                              28    0.13                                                                              87    10   10   81   0                                                    0.25                                                                              80    13   27   89   0                                                    0.50                                                                              60    40   27   46   0                                                    1.0 43    53   40   30   0                                              61    0.13                                                                              97    0    0    99   0                                                    0.25                                                                              87    17   13   77   0                                                    0.50                                                                              63    30   27   54   0                                                    1.0 37    60   47   31   0                                              Trifluralin                                                                         0.96                                                                              73    30   17   60   0                                              Metribuzin                                                                          0.49                                                                              90    13   7    87   0                                              Untreated 100   0    0    100  0                                              Control                                                                       Cotton                                                                         1    0.13                                                                              83    17   17   96   0                                                    0.25                                                                              80    23   30   85   0                                                    0.50                                                                              70    33   30   80   0                                                    1.0 43    53   43   38   0                                               6    1.0 90    10   0    97   0                                                    2.0 87    13   3    104  0                                              28    0.13                                                                              97    3    0    112  0                                                    0.25                                                                              90    10   23   92   0                                                    0.50                                                                              80    27   13   97   0                                                    1.0 90    13   20   84   0                                              61    0.13                                                                              93    7    0    117  0                                                    0.25                                                                              73    17   7    97   0                                                    0.50                                                                              90    17   7    94   0                                                    1.0 80    17   23   94   0                                              Trifluralin                                                                         0.96                                                                              93    20   23   108  0                                              Metribuzin                                                                          0.49                                                                              37    73   67   24   0                                              Control   100   0    0    100  0                                              Corn                                                                           1    0.13                                                                              93    30   27   86   0                                                    0.25                                                                              90    33   30   88   0                                                    0.50                                                                              87    43   37   89   0                                                    1.0 77    57   60   85   37                                              6    1.0 97    3    3    94   0                                                    2.0 93    13   3    90   3                                              28    0.13                                                                              97    7    10   94   0                                                    0.25                                                                              83    33   17   84   0                                                    0.50                                                                              90    13   20   79   0                                                    1.0 90    27   27   91   0                                              61    0.13                                                                              97    17   3    95   0                                                    0.25                                                                              93    13   7    95   0                                                    0.50                                                                              87    30   13   86   0                                                    1.0 90    40   30   83   0                                              Trifluralin                                                                         0.96                                                                              77    47   37   74   3                                              Metribuzin                                                                          0.49                                                                              77    60   57   84   0                                              Control   100   0    0    100  0                                              __________________________________________________________________________

                                      TABLE VII                                   __________________________________________________________________________    Compound    %       %        %                %                               of          Weed Control                                                                          Weed Control                                                                           Weed Control                                                                          %        Weed Control                                                                          %                       Example                                                                             Rate  Annual Broad-                                                                         Other Broad-                                                                           Southern                                                                              Weed Control                                                                           Rhynchelytrum                                                                         Weed Control            No.   kg/ha leaves  leaves   Sanbur  Goosegrass                                                                             Roseum  Sida                    __________________________________________________________________________                                                          Spp.                     1    0.13  7       0        7       17       0       10                            0.25  83      10       27      37       20      10                            0.50  90      17       57      60       27      0                             1.0   93      60       73      80       70      13                       6    1.0   0       0        20      63       0       0                             2.0   7       0        30      37       0       0                       28    0.13  0       0        20      7        7       3                             0.25  13      0        43      60       7       0                             0.50  53      3        27      33       0       0                             1.0   40      10       40      33       23      10                      61    0.13  0       0        0       0        0       0                             0.25  0       0        0       0        0       0                             0.50  73      10       13      17       37      0                             1.0   73      30       30      85       37      0                       Trifluralin                                                                         0.96  53      7        97      97       87      0                       Metribuzin                                                                          0.49  30      27       70      87       83      70                      Control     0       0        0       0        0       0                       __________________________________________________________________________

A field study was carried out in Canada to determine the herbicidalefficacy and crop tolerance of various preferred benzamides alone and incombination with the commercial herbicide trifluralin. The herbicideswere applied as an aqueous spray, and the field plots were seeded to thecereal grain barley and various weed species, after which the herbicideswere soil incorporated utilizing a diamond harrow. Crop injury ratingswere made visually on a scale of 0-10, with 0 being no injury and 10being plant death. All observations reported were made twenty-six dayspost seeding and application, except crop yield data were determinedeighty-four days following treatment. The percent of weed control ofvarious weed species occurring in cereal crops such as barley weredetermined by visual comparison with untreated control plots. Theresults of the field test are present below in Table VIII.

                                      TABLE VIII                                  __________________________________________________________________________    Barley                                                                        Compound of                                                                            Rate  Crop                                                                              % Crop                                                                              % Weed Control                                                                         % Weed Control                                                                          % Weed Control                                                                         % Weed Control           Example No.                                                                            kg/ha Injury                                                                            Yield White Mustard                                                                          Redroot Pigweed                                                                         Lambsquarter                                                                           Green                    __________________________________________________________________________                                                         Smartweed                Trifluralin                                                                            0.7   0   119   0        95        40       0                        Control        0   100   0        0         0        0                        6        1.1   0   143   95       85        40       20                                2.2   0   111   95       95        75       0                        6 + Trifluralin                                                                        1.1 + 0.7                                                                           0   119   90       95        40       0                                 1.68 + 0.7                                                                          0   107   90       95        40       0                                 2.2 + 0.7                                                                           0    99   100      95        70       20                       27       1.1   0   147   100      90        50       20                                2.2   0    87   100      95        75       0                        27 + Trifluralin                                                                       0.56 + 0.7                                                                          0   123   95       90        20       0                                 1.1 + 0.7                                                                           0   107   95       90        50       0                                 1.68 + 0.7                                                                          0   135   100      95        40       0                                 2.2 + 0.7                                                                           0   107   95       95        40       10                       28       1.1   0   107   100      70        45       10                                2.2   0   103   100      95        75       0                        28 + Trifluralin                                                                       0.56 + 0.7                                                                          0   119   95       95        40       0                                 1.1 + 0.7                                                                           0   111   95       75        50       0                                 1.68 + 0.7                                                                          0   139   95       95        50       0                                 2.2 + 0.7                                                                           0   119   100      95        40       10                       101      1.1   0   111   95       80        30       0                                 2.2   0   111   95       95        70       0                        101 + Trifluralin                                                                      0.56 + 0.7                                                                          0   119   95       90        40       0                                 1.1 + 0.7                                                                           0   119   85       95        75       0                                 168 + 0.7                                                                           0   131   95       95        50       0                                 2.2 + 0.7                                                                           0   123   95       95        40       10                       __________________________________________________________________________

As can be seen from the data presented above, the benzamides of thisinvention exhibit a broad-spectrum of herbicidal activity. Some of thecompounds also have demonstrated a certain amount of insecticidalactivity. A further important embodiment of this invention is aherbicidal method for killing and controlling the growth of unwantedvegetation which comprises applying to the locus where vegetativecontrol is desired a herbicidally effective amount of a benzamide ofthis invention. Since the compounds are capable of killing and retardingthe growth of a number of weeds and undesirable plants which commonlygrow in areas used for growing desired crops such as cereal grains andthe like, the method of the invention is particularly applicable topractice in such crops. For example, the benzamides are very effectivein killing and retarding the growth of weeds such as barnyardgrass,lambsquarter, yellow foxtail, fall panicum, wild buckwheat, crabgrass,mustard, pigweed, cocklebur, velvet-leaf, jimsonweed, morningglory,ragweed, zinnia and a number of other vegetative species which are knownto comprise unwanted weed and grass vegetation. The compounds are alsoeffective in controlling the growth of perennial weeds. For example, thecompounds of Example 1 and of Example 6 have demonstrated effectivenessagainst noxious plants such as silverleaf nightshade. While thecompounds are toxic to such undesired weeds and grasses, they do notadversely affect the growth of desirable crops such as the cerealgrains, for example wheat, barley, oats and rice. The compounds can alsobe employed in combating undesired vegetative growth in crops such ascorn, soybeans, peanuts, cotton and related crops. The compound ofExample 6 appears particularly suited, for instance, in controllingweeds in cotton, soybeans, peanuts, peas and the like. The herbicidalselectivity of the benzamides is an important benefit to be realized inthe practice of the invention. The compounds can also be utilized in thecontrol of unwanted vegetation in non-crop land, for instance in achemical fallow land program, particularly in fallow wheatland and thelike.

The benzamides of the invention can also be employed in combination withany of several known and commonly used herbicides. For example, apreferred method of herbicidal control according to this inventionemploys a benzamide of the invention used in conjunction with one ormore other herbicides, ideally one or more grass herbicides, for examplea dinitroaniline herbicide such as trifluralin, butralin, dinitramine,nitralin, profluralin, prodiamine, oryzalin, isopropalin, ethalfluralin,benefin, fluchloralin, pendimethalin, and the like. Other herbicides tobe employed in combination with the present benzamides include alachlor,ametryn, amitrole, atrazine, bentazon, bifenox, butachlor, butam,buthidazole, chloramben, chlorbromuron, cyanazine, dichloroprop,dinoseb, fenac, linuron, methazole, metolachlor, metribuzin, nitrofen,pebulate, prometon, prometryn, propachlor, simazine, terbutryn,triallate, trichopyr, propanil and the like.

The use of the benzamides of this invention in combination with otherherbicides provides for an even broader range of weed control thangenerally can be realized with either the benzamides alone or the otherherbicides such as trifluralin alone. Such combinations are particularlypreferred when practicing the method in cereal grains.

The benzamides provided herein can also be applied in conjunction withagricultural chemicals which are utilized to control pests other thanunwanted vegetative growth. The benzamides of this invention lendthemselves well to combination with other agricultural chemicals such asinsecticides, fungicides, nematicides, and other herbicides as may bedesirable and convenient.

In carrying out the method of this invention, a benzamide of theinvention can be applied post-emergence to soil or to the foilage ofplants whose growth is to be controlled, or pre-emergence to the locuswhere the growth of unwanted vegetation is to be controlled. A preferredherbicidal method comprises application of the benzamide pre-emergence.The compounds can be applied to the surface of soil in which the growthof unwanted weeds and grasses is to be eliminated or retarded, or ifdesired the compounds can be incorporated into the soil, for example byuse of conventional tillage equipment such as the disc, harrow or thelike. Soil incorporation or surface application may be employed when thebenzamides are utilized in combination with other herbicides such astrifluralin or the like. Also, pre-emergence soil incorporation ispreferred for compounds having less than desired activity when surfaceapplied but not incorporated.

The compounds of the invention are effective in selectively killing andcontrolling the growth of unwanted vegetation when applied at aherbicidally-effective rate. In carrying out the method of theinvention, and in the case of using the benzamides as pre-emergenceherbicides, the active ingredient will be applied to the locus whereweed control is desired at a rate of about 0.05 to about 15 pounds peracre, and more desirably at a rate of about 0.1 to about 5 pounds peracre. The most active compounds will generally be applied at about 0.1to about 2 pounds per acre. It will of course be understood by thosehaving skill in the herbicidal art that such rates of application mayvary, depending upon several factors, including the type of locus beingtreated, the particular benzamide being utilized, the particular weedsor grasses to be killed or controlled, whether the method is beingpracticed in cropland or fallow land, whether or not the herbicide isbeing incorporated into the soil, whether or not the benzamide is beingutilized in conjunction with other agricultural chemicals, for instanceother herbicides such as pendimethalin or simazine. Moreover, while theabove-suggested rates are preferred for pre-emergent weed control, thecompounds can be applied post-emergence at rates of about 1 to about 20pounds per acre, and more preferably at about 2 to about 10 pounds peracre.

The herbicidal method provided by this invention can be carried outemploying any of the benzamide herbicides defined herein, but as notedearlier, the method is preferably practiced employing an N-isoxazolyl orthiadiazolyl-2,6-dialkoxybenzamide. An especially preferred methodemploys a benzamide selected fromN-[3-(1,1-dimethylethyl)-5-isoxazolyl]-2,6-dimethoxybenzamide,N-[3-(1-ethyl-1-methylpropyl)-5-isoxazolyl]2,6-dimethoxybenzamide,N-[5-(1-ethyl-1-methylpropyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide,N-[3-(1-ethylcyclohexyl)-5-isoxazolyl]-2,6-dimethoxybenzamide andN-[5-(1-ethyl-1-methylpropyl)-3-isoxazolyl]-2,6-dimethoxybenzamide.Another preferred herbicidal method employs a pyridazinyl benzamide, forinstanceN-[6-(1-ethyl-1-methylpropyl)-pyridazin-3-yl]-2,6-dimethoxybenzamide, orthe like. Such compounds can be employed alone at rates of about 0.1 toabout 2 pounds per acre, or if desired they can be employed incombination with other herbicides such as trifluralin, ametryn, alachloror the like. When utilized in combination with other herbicides, theexact rate of application for each of the component herbicides will bedetermined by several factors, including the specific weeds and grassesto be controlled, the particular herbicides used in combination, theweed population, and related factors. Generally, the benzamides will beemployed in combination with other herbicides in a ratio of about one toabout five parts by weight of benzamide and about five to about one partby weight of another herbicide. A preferred combination will contain thecomponent herbicides in a weight ratio of about one to one. Suchcombination will be applied at a rate which is effective to control theunwanted vegetation to the desired degree. The respective herbicides canbe applied separately or as a single mixture, for example, a tank mix orthe like.

The benzamides of this invention ideally are suitably formulated for useas described above. Herbicidal formulations comprising a benzamideherbicide of the invention admixed with an agronomically acceptablediluent, excipient or carrier therefor thus form a further importantembodiment of the invention. Such compositions will typically containfrom about 1 to about 95 percent by weight of active herbicide, and moregenerally about 10 to about 60 percent. The formulations may take theform of solid powders, dusts, granules; aqueous or non-aqueous sprays ordrenches; concentrates, for example emulsifiable concentrates and thelike; wettable powders, and any of the other forms commonly found in theagriculture art for herbicides.

Agronomically acceptable carriers, diluents and excipients commonlyutilized to form powders, dusts, granules and the like include talc,diatomaceous earth, silica, pyrophyllite, attapulgite clays and thelike. It is often desirable to formulate a compound of the invention asa granule for convenient pre-emergence application to soil. Suchformulation generally is prepared by dissolving the benzamide herbicidein a suitable solvent such as kerosene or aromatic naphtha, and applyingthe solution to a carrier such as montmorillonite clay granules or thelike. Another procedure which can be employed comprises simplydispersing an active ingredient in a dough composed of a suitablecarrier, for instance damp clay, and then drying and grinding the clayto provide the formulated granules at the desired particle size.

The benzamides of the invention are also conveniently formulated asconcentrated compositions which are diluted prior to application, forinstance by the addition of water or other suitable diluent to make adispersion, emulsion or the like. Typical concentrated formulationswhich are in the form of solids are wettable powders. Wettable powderscomprise a finely-divided intimate mixture of an inert carrier orexcipient, a benzamide herbicide, and a suitable surfactant. Commonlyutilized inert carriers which are agronomically acceptable include thediatomaceous earths, the various clays such as attapulgite clays orkaolin clays, or silica. Surfactants generally are present in about 0.5to about 10 percent by weight of the wettable powder, with the benzamideherbicide being present in about 10 to about 60 percent by weight. Anyof several known surfactants can be employed in the wettable powderformulations, including any of the sulfonated lignins, the condensednaphthalenesulfonates, the alkylbenzenesulfonates, the alkyl sulfates,as well as the nonionic surfactants such as the ethylene oxide adductsof phenols. The wettable powders which are thus comprised generally arediluted with water or the like prior to application, so that thedispersion or final mixture contains from about 0.1 to about 5.0 percentby weight of the active benzamide herbicide. Such formulation is thenapplied as a spray or the like by conventional sprayers or otheragricultural chemical applicators.

Another commonly utilized formulation type to be employed with thebenzamide herbicides are the emulsifiable concentrates. Suchformulations are comprised of a benzamide herbicide admixed with acarrier such as a water immiscible organic solvent and an emulsifyingagent. Water miscible cosolvents may be utilized in conjunction with theimmiscible solvent to improve solubility of the benzamide. Commonly usedsolvents include toluene, xylene, chlorotoluene, benzene, methylisobutyl ketone, cyclohexanone, naphtha and the like. Aqueoussuspensions employing water as a diluent also are contemplated.Emulsifiers which can be employed include the common surfactants andblends of surfactants, for example the alkyl and aryl sulfonates,ethoxylated alkyl phenols, ethoxylated alkyl ethers, the nonoxynols,oxysorbics, allinols, allinates and other nonionic and anionicsurfactants. The surfactant may be present in about 0.5 to about 10percent by weight. Such concentrates, like the wettable powderformulations, are diluted prior to application, for instance by theaddition of the appropriate amount of water to provide a mixture havingthe desired concentration of active ingredient.

As noted above, the benzamides provided herein are especially useful incombination with other herbicides in order to achieve the range andspecificity of weed control desired. A typical method for employing acombination of benzamide herbicide and another herbicide such astrifluralin, terbutryn, or the like, comprises mixing and diluting justprior to application the individual formulations of the respectiveindividual herbicides. The mixing can be carried out, for example, inthe tank of a conventional spraying apparatus. A typical combination ofa benzamide of this invention with a herbicide such as trifluralin canbe prepared by tank mixing at the site of application a wettable powderformulation of benzamide with an emulsifiable concentrate oftrifluralin. Such tank-mixed combination will be applied to soil and ifdesired incorporated therein at a rate such that each active ingredientis present at about 0.5 to about 2 pounds per acre. Such combinationprovides excellent pre-emergence control of a wide variety of unwantedvegetative species.

The following examples further illustrate typical herbicidalcompositions and their use as provided by this invention.

EXAMPLE 178

    ______________________________________                                        Wettable Powder                                                                                    Concentration by                                         Ingredient           Weight (Percent)                                         ______________________________________                                        N--[3-(1-ethyl-1-methylpropyl)-5-                                                                  50                                                       isoxazolyl]-2,6-dimethoxybenzamide                                            (the compound of Example 1)                                                   Igepal CA-630, a polyoxyethylene octyl                                                              5                                                       phenol nonionic wetting agent -                                               GAF Corporation                                                               Bardens Clay         45                                                       ______________________________________                                    

The benzamide herbicide is blended to uniformity with the adjuvants andmilled to form a free flowing powder that will be wetted and suspensiblein water at or near the site of application to form a sprayable mixture.The formulation is sprayed on the locus where vegetative control isdesired at a volume so that the active ingredient is applied at about0.1 to about 2 pounds per acre.

EXAMPLE 179

    ______________________________________                                        Wettable Powder                                                               Ingredient            Percent by Weight                                       ______________________________________                                        N--[5-(1-ethyl-1-methylpropyl)-1,3,4-                                                               50                                                      thiadiazol-2-yl]-2,6-dimethoxybenzamide                                       (the compound of Example 61)                                                  Stepanol ME, a technical grade of sodium                                                            4                                                       lauryl sulfate, Stepan Chemical Corp.                                         Reax 45L, a lignosulfonate                                                                          6                                                       dispersant, Westvaco Corporation                                              Zeolex-7, a precipitated hydrated                                                                   2                                                       silicate, J.M. Huber Corporation                                              Barden Clay, a hydrated aluminum                                                                    38                                                      silicate, J.M. Huber Corporation                                              ______________________________________                                    

The ingredients are blended and pulverized to provide a free flowingpowder that can be suspended in water for convenient spray application.The aqueous spray will be applied at about 5 to about 50 gallons peracre for an application rate of about 1 to about 5 pounds per acre ofactive benzamide.

EXAMPLE 180

    ______________________________________                                        Aqueous Suspension                                                            Ingredient            Percent by Weight                                       ______________________________________                                        N--[3-(1,1-dimethylethyl)-5-                                                                        43                                                      isoxazolyl]-2,6-dimethoxybenzamide                                            (the compound of Example 6)                                                   Polyfon H, an anionic lignosulfonate                                                                4                                                       wetting agent and dispersant,                                                 Westvaco Corporation                                                          Min-u-gel 200, a clay-type gelling                                                                  2                                                       agent, The Floridin Company                                                   Antifoam C            0.05                                                    Dow Corning Corp.                                                             Water                 50.95                                                                         100.00%                                                 ______________________________________                                    

The ingredients are mixed and finely ground to uniformity to provide asuspension of active ingredient. The suspension is diluted withadditional water and applied as a spray to the locus to be treated.

EXAMPLE 181

    ______________________________________                                        Granular Formulation                                                          Ingredient             Percent by Weight                                      ______________________________________                                        N--[5-[1,1-dimethyl-2-(methylthio)-                                                                  5                                                      ethyl)-1,3,4-thiadiazol-2-yl]-                                                2,6-dimethoxybenzamide                                                        (the compound of Example 64)                                                  Heavy aromatic naphtha 5                                                      Florex 30/60, granular clay, Floridin Co.                                                            90                                                     ______________________________________                                    

The benzamide is substantially dissolved in the heavy aromatic naphthaand sprayed onto clay granules of substantially uniform size, ideallyless than about 1.0 cubic millimeter, preferably of the 30/60 sizerange. The granular formulation is surface applied to soil so that theactive ingredient is present at about 3 to about 10 pounds per acre.

EXAMPLE 182

    ______________________________________                                        Dust Formulation                                                              Ingredient           Percent by Weight                                        ______________________________________                                        N--[3-(1-ethyl-1-methylpropyl)-1H--                                                                 5                                                       pyrazol-5-yl]-2,6-dimethoxybenzamide                                          (the compound of Example 115)                                                 Diatomite, a diatomaceous earth, Witco                                                             95                                                       Chemical Corporation, Inorganic                                               Specialties Division                                                          ______________________________________                                    

The benzamide herbicide is dry mixed with the diatomaceous earthdiluent. The mixture is ground to a fine powder of uniform particle sizeof about 10 to about 40 microns. If a more concentrated mixture isemployed (e.g. about 30 to about 50% active), the formulation can bediluted by the addition of additional excipient such as silica or clayat the site of application. The dust thus formed is surface applied byconventional ground equipment, to the soil surface where vegetativecontrol is desired, or if desired the dust can be applied byconventional aircraft units.

EXAMPLE 183

    ______________________________________                                        Tank-Mix Composition                                                          Ingredient             Percent by Weight                                      ______________________________________                                        N--[5-(1-ethyl-1-methylpropyl)-4H--                                                                  60                                                     1,2,4-triazol-3-yl]-2,6-dimethoxy                                             benzamide (the compound of Example                                            118) 50WP                                                                     N,N--diethyl-2,6-dinitro-3-amino-4-                                                                  40                                                     trifluoromethyl aniline (dinitramine) 2EC                                     ______________________________________                                    

A wettable powder formulation containing 50% by weight of the benzamideof Example 118 is dispersed in water and the mixture is agitated whilean aqueous suspension of emulsifiable concentrate (2 lbs/gal)formulation of the dinitroaniline herbicide is added. The resultingmixture is agitated and sprayed on the soil surface and incorporatedtherein at the rate of about 1 pound per acre of benzamide and about0.67 pound per acre of the dinitroaniline. The soil can then be seededto soybeans or the like, and the crop is grown substantially free ofunwanted vegetation such as crabgrass, fall panicum, purslane and thelike. The yield and quality of the desired crop is thereby greatlyimproved.

EXAMPLE 184

    ______________________________________                                        Tank-mix Composition                                                          Ingredient          Percent by Weight                                         ______________________________________                                        N--[5-(1-ethyl-1-methylpropyl)-1,3,4-                                                             50                                                        thiadiazol-2-yl]-2,6-diethylbenzamide                                         (the compound of Example 63) 50WP                                             N,N--di- -n-propyl-2,6-dinitro-3-amino-                                                           50                                                        4-trifluoromethylaniline (prodiamine)                                         50WP                                                                          ______________________________________                                    

A 50% wettable powder formulation of the benzamide is mixed with anaqueous suspension of a 50% wettable powder of the prodiamine. Themixture is agitated and sprayed on soil where weed control is desired.The rate of application will be about 30 gallons per acre such that eachactive ingredient is applied at about 0.75 pounds per acre. The mixtureis preferably incorporated into the soil, for instance by discing, andthen the soil is planted to cotton, soybeans, sugarcane, or the like.

EXAMPLE 185

    ______________________________________                                        Tank-mix Composition                                                          Ingredient           Percent by Weight                                        ______________________________________                                        N--[5-(1-propylcyclohexyl)-1,3,4-                                                                  30                                                       thiadiazol-2-yl]-2,6-dimethoxy                                                benzamide (the compound of                                                    Example 105) 30WP                                                             N,N--di- -n-propyl-2,6-dinitro-4-                                                                  70                                                       trifluoromethylaniline (trifluralin) 4EC                                      ______________________________________                                    

A 30% wettable powder formulation of the benzamide of Example 105 isdispersed in water and agitated while an emulsifiable concentrate (4lbs/gal) formulation of trifluralin is added portion-wise. Thetank-mixed aqueous mixture is sprayed onto soil and incorporated for thecontrol of chickweed, kochia, pigweed, Russian thistle, lambsquartersand the like. The treated soil can be seeded to cereal grains such aswheat, rye, oats, barley, and the like. Such crops grow substantiallyunaffected by undesired vegetative growth.

EXAMPLE 186

    ______________________________________                                        Wettable Powder                                                                                   Concentration by                                          Ingredient          Weight (Percent)                                          ______________________________________                                        N--[6-(1-ethyl-1-methylpropyl)-                                                                   51.5                                                      pyridazin-3-yl]-2,6-                                                          dimethoxybenzamide                                                            (the compound of Example 157)                                                 Sellogen HR wetting agent                                                                         5.0                                                       (Diamond Shamrock Corp.)                                                      Polyfon O, lignosulfonate                                                                         5.0                                                       dispersant (Westvaco Corp.)                                                   Zeolex 7, a precipitated                                                                          5.0                                                       hydrated silica bulking                                                       agent, (J.M. Huber Corp)                                                      Barden Clay         33.5                                                                          100.0                                                     ______________________________________                                    

EXAMPLE 187

    ______________________________________                                        Wettable Powder                                                                                  Concentration by                                           Ingredient         weight (Percent)                                           ______________________________________                                        N--[6-(1,1-dimethylethyl)-                                                                       50.0                                                       pyridazin-3-yl]-2,6-                                                          dimethoxythiobenzamide                                                        Sellogen HR        5.0                                                        Polyfon 0          5.0                                                        Barden Clay        40.0                                                                          100.0                                                      ______________________________________                                    

EXAMPLE 188

    ______________________________________                                        Aqueous Suspension                                                            Ingredient        Percent by Weight                                           ______________________________________                                        N--[3-(1,1-dimethylethyl)-                                                                      45.00                                                       5-isoxazolyl]-2,6-diethoxy-                                                   thiobenzamide                                                                 Emulphor, polyoxyethylated                                                                      5.00                                                        vegetable oil wetting agent                                                   (GAF Corp.)                                                                   Atflow, suspending agent                                                                        5.00                                                        (ICI Americas Inc..)                                                          Water             45.00                                                                         100.00%                                                     ______________________________________                                    

EXAMPLE 189 Combination use

A 4EC formulation of trifluralin is applied to soil prior to seeding.The trifluralin, at about 0.5 pound per acre, is incorporated into thesoil by use of a double disc. The soil is seeded to soybeans, and then a50% wettable powder formulation ofN-[3-(1,1-dimethylethyl)-5-isoxazolyl]-2,6-dimethoxybenzamide (thecompound of Example 6) is suspended in water and surface sprayed on theplanted soil. The active benzamide is present at about 1.5 pounds peracre. The treatment permits the growth of the desired soybeans withoutundesirable growth of weeds such as lambsquarter, pigweed, and the like.

A particularly preferred herbicidal method according to this inventionemploys the benzamide of Example 1, namelyN-[3-(1-ethyl-1-methylpropyl)-5-isoxazolyl]-2,6-dimethoxybenzamide. Suchcompound is especially effective when employed in combination with otherherbicides such as trifluralin. The use of such benzamide, as well asthe combination, is contemplated to be of major importance in thecontrol of unwanted vegetation in cereal grains such as wheat, oats,barley and the like.

The benzamides provided by this invention are also useful in the controlof unwanted vegetation such as broadleaf weeds in orchards and arbors.The compounds have demonstrated excellent selective herbicidal activityin citrus crops such as orange and lemon orchards. The compounds arealso expected to be useful in the control of weeds in vines such asgrapes and the like, as well as in crops such as sugarcane. Thecompounds additionally have exhibited plant growth regulator activity,for instance in the form of improved yields of grain and the like and inreducing stalk height. The compounds also have demonstrated utility asaquatic herbicides, and can thus be employed in the control of sagopondweed, duckweed, naiad, milfoil, cabomba, hydrilla verticillata, andsimilar weeds that grow in streams, ponds and other water areas. Thecompound of Example 1, for instance, when evaluated as an aquaticherbicide at 1.0 ppm, caused from 87 to 90 percent control of hydrilla,milfoil and sago at fourteen days post treatment. Because of theirherbicidal activity against aquatic weeds, the compounds are well suitedto the control of weeds in crops such as rice.

I claim:
 1. An N-aryl benzamide of the formula ##STR42## wherein: R¹ ishydrogen or C₁ -C₄ alkoxy;R² is C₁ -C₄ alkylthio or C₁ -C₄ alkoxy; R³ isC₁ -C₄ alkyl, C₁ -C₄ alkylthio, or C₁ -C₄ alkoxy; R⁵ is ##STR43##wherein: R⁶ is C₁ -C₄ alkyl, C₂ -C₄ alkenyl, C₂ -C₄ alkynyl, C₁ -C₆alkoxy, or C₁ -C₆ alkylthio; y is an integer from 0 to 4; R⁷ and R⁸independently are C₁ -C₁₃ alkyl; R⁹ and R¹⁰ independently are hydrogen,halogen, C₁ -C₄ alkyl, or C₂ -C₄ alkenyl; Q¹ and Q² are CH₂ ; and theagronomically acceptable salts thereof.
 2. A compound of claim 1selected from the group consistingof:N-[5-(1,1-dimethyl-2-(methylthioethyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide;N-[5-(2-methoxy-1,1-dimethylethyl)-1,3,4-thiadiazole-2-yl]-2,6-dimethoxybenzamide;N-[5-(1,1-dimethyl-3-butenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamideN-[5-(2-chloro-1,1-dimethylethyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide;N-[5-(2,2-dimethylpropyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide;N-[5-(1-methylcyclobutyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide;N-[5-(1,1-dimethyl-2-propenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide;N-[5-(1-ethyl-1-methypentyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide;N-[5-(1-ethyl-1-propylbutyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide;N-[5-(1-ethyl-1,3-dimethylbutyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide;N-[5-(1,1-dimethyl-2-methoxypropyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide;N-[5-(1-methyl-1-methylthiopropyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide;N-[5-(1-ethyl-1-methylthiopropyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide;N-[5-(1-methyl-1-methylthiomethylpropyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide.3. The compound of claim 1, said compound beingN-[5-(1-ethyl-1-methylpropyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide.4. The compound of claim 1, said compound beingN-[5-(1,1-diethylpropyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide.5. The compound of claim 1, said compound beingN-[5-(1,1-dimethylhexyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide.6. The compound of claim 1, said compound beingN-[5-(1-ethylpentyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide. 7.The compound of claim 1, said compound beingN-[5-(1-methylcyclohexyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide.8. The compound of claim 1, said compound beingN-[5-(1-ethyl-1-methylbutyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide.9. The compound of claim 1, said compound beingN-[5-(1-methylcyclopentyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide.10. The compound of claim 1, said compound beingN-[5-(1,2-dimethylpropyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide.11. The compound of claim 1, said compound beingN-[5-(1-ethylcyclohexyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide.12. The compound of claim 1, said compound beingN-[5-(1,1-diethylbutyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide.13. The compound of claim 1, said compound beingN-[5-(1-isopropylcyclohexyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide.14. The compound of claim 1, said compound beingN-[5-(1,1,2-trimethylpropyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide.15. The compound of claim 1, said compound beingN-[5-(1-ethylcyclopentyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide.16. The compound of claim 1, said compound beingN-[5-(1-methyl-1-propylbutyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide.17. The compound of claim 1, said compound beingN-[5-(1,1,2,2-tetramethylpropyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide.18. The compound of claim 1, said compound beingN-[5-(1,1-dimethylpropyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide.19. The compound of claim 1, said compound beingN-[5-(1-propylcyclohexyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide.20. The compound of claim 1, said compound beingN-[5-(1,1-dimethylpentyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide.21. The compound of claim 1, said compound beingN-[5-(1-n-propylcyclopentyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide.22. The compound of claim 1, said compound beingN-[5-(1,1,2-trimethylbutyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide.23. The compound of claim 1, said compound beingN-[5-(1,1-dimethylethyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide.24. A compound of claim 1 wherein: ##STR44## R⁵ is ##STR45## R⁶ is C₁-C₄ alkyl, C₂ -C₄ alkenyl, or C₂ -C₄ alkynyl;R⁷ is C₁ -C₄ alkyl; and R⁸is C₁ -C₁₃ alkyl.